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                                                                    Exhibit 10.1

                            VIROPHARMA INCORPORATED
                               STOCK OPTION PLAN

                    Originally Effective September 20, 1995
                 Amended and Restated, Effective March 3, 1998
                       As Amended Through June 22, 2000.
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                            VIROPHARMA INCORPORATED
                               STOCK OPTION PLAN


     Section 1.  Purposes.
                 --------

     The ViroPharma Incorporated 1995 Stock Option Plan was originally effective
September 20, 1995.  The ViroPharma Incorporated Stock Option Plan (the "Plan"),
effective March 13, 1998, is an amendment and restatement of this prior plan.
The Plan was most recently amended on March 13, 2000.  The purposes of the Plan
are to: (a) further the growth and success of ViroPharma Incorporated (the
"Company") and its Subsidiaries by enabling selected employees, directors,
consultants and advisors of the Company and any Subsidiaries to acquire shares
of common stock of the Company, thereby increasing their personal interest in
such growth and success and (b) to provide a means of rewarding outstanding
performance of such persons to the Company and/or its Subsidiaries.  The Options
granted pursuant to the Plan are intended to constitute either Incentive Stock
Options within the meaning of Section 422 of the Code, or non-qualified stock
options, as determined by the Board or the Committee at the time of award.  The
type of Options awarded will be specified in the Option Agreement between the
Company and the Optionee.  The terms of the Plan shall be incorporated in the
Option Agreement to be executed by the Optionee.

     Section 2.  Definitions
                 -----------

     (a) "Affiliate" shall mean, with respect to a Person, a Person that
          ---------
directly or indirectly controls, or is controlled by, or is under common control
with such Person.

     (b) "Award" shall mean a grant of an Option or Options to an Eligible
          -----
Person pursuant to the provisions of this Plan.  Each separate grant of an
Option or Options to an Eligible Person and each group of Options which vests on
a separate date, is treated as a separate Award.

     (c) "Board" shall mean the Board of Directors of the Company, as
          -----
constituted from time to time.

     (d) "Change of Control" shall mean the happening of an event, which shall
          -----------------
be deemed to have occurred upon the earliest to occur of the following events:

         (i)  the date the stockholders of the Company (or the Board, if
              stockholder action is not required) approve a plan or other
              arrangement pursuant to which the Company will be dissolved or
              liquidated, or

         (ii) the date the stockholders of the Company (or the Board, if
              stockholder action is not required) approve a definitive agreement
              to sell or otherwise dispose of all or substantially all of the
              assets of the Company, or

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       (iii)  the date the stockholders of the Company (or the Board, if
              stockholder action is not required) and the stockholders of the
              other constituent corporations (or their respective boards of
              directors, if and to the extent that stockholder action is not
              required) have approved a definitive agreement to merge or
              consolidate the Company with or into another corporation, other
              than, in either case, a merger or consolidation of the Company in
              which holders of shares of the Company's voting capital stock
              immediately prior to the merger or consolidation will have at
              least 50% of the ownership of voting capital stock of the
              surviving corporation immediately after the merger or
              consolidation (on a fully diluted basis), which voting capital
              stock is to be held in the same proportion (on a fully diluted
              basis) as such holders' ownership of voting capital stock of the
              Company immediately before the merger or consolidation, or

        (iv)  the date any entity, Person or group (within the meaning of
              Section 13(d)(3) or Section 14(d)(2) of the Exchange Act), other
              than (A) the Company, or (B) any of its Subsidiaries, or (C) any
              employee benefit plan (or related trust) sponsored or maintained
              by the Company or any of its Subsidiaries or (D) any Affiliate (as
              such term is defined in Rule 405 promulgated under the Securities
              Act) of any of the foregoing, shall have acquired beneficial
              ownership of, or shall have acquired voting control over more than
              50% of the outstanding shares of the Company's voting capital
              stock (on a fully diluted basis), unless the transaction pursuant
              to which such Person, entity or group acquired such beneficial
              ownership or control resulted from the original issuance by the
              Company of shares of its voting capital stock and was approved by
              at least a majority of Directors who shall have been either
              members of the Board on the date that this Plan was originally
              adopted by the Board or members of the Board for at least twelve
              (12) months prior to the date of such approval, or

         (v)  the first day after the date of this Plan when Directors are
              elected such that there shall have been a change in the
              composition of the Board such that a majority of the Board shall
              have been members of the Board for less than twelve (12) months,
              unless the nomination for election of each new Director who was
              not a Director at the beginning of such twelve (12) month period
              was approved by a vote of at least sixty percent (60%) of the
              Directors then still in office who were Directors at the beginning
              of such period, or

        (vi)  the date upon which the Board determines (in its sole discretion)
              that based on then current available information, the events
              described in clause (iv) are reasonably likely to occur.

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          (e) "Code" shall mean the Internal Revenue Code of 1986, as amended.
               ----

          (f) "Committee" shall mean a committee appointed by the Board in
               ---------
accordance with Section 4(a) of the Plan, and if one is appointed, then such
committee shall possess all of the power and authority of, and shall be
authorized to take any and all actions required to be taken hereunder by, and
make any and all determinations required taken hereunder by, the Board.

          (g) "Common Stock" shall mean common stock of the Company, $.002 par
               ------------
value per Share.

          (h) "Company" shall mean ViroPharma Incorporated.
               -------

          (i) "Company Plan" means any restricted stock, stock bonus, stock
               ------------
option or other compensation plan, program or arrangement established or
maintained by the Company or an Affiliate.

          (j) "Director" shall mean an individual who is a member of the Board
               --------
of Directors of the Company.

          (k) "Disability" shall mean a mental or physical disability of an
               ----------
Eligible Person which renders such Eligible Person unable to perform the full
extent of his duties and responsibilities by reason of his illness or incapacity
for a period of 90 consecutive days or longer, or for 90 days during any six-
month period.

          (l) "Eligible Person" shall mean any person employed by the Company or
               ---------------
any of its Subsidiaries. Additionally, the term "Eligible Person" shall include
advisors and consultants to the Company or any Subsidiary, as well as Directors
and members of the board of directors of a Subsidiary; provided that Options to
Eligible Persons who are not employees of the Company or any of its Subsidiaries
shall be limited to non-qualified stock options.

          (m) "Exchange Act" shall mean the Securities Exchange Act of 1934, as
               ------------
amended.

          (n) "Fair Market Value Per Share" shall mean the fair market value of
               ---------------------------
a share of Common Stock, as determined pursuant to Section 8 hereof.

          (o) "Incentive Stock Option" shall mean an Option which is an
               ----------------------
incentive stock option as described in Section 422 of the Code.

          (p) "Non-Employee Director" shall have the meaning set forth in Rule
               ---------------------
16b-3(b)(3)(i) promulgated by the Securities and Exchange Commission under the
Exchange Act, or any successor definition adopted by the Securities and Exchange
Commission; provided, however, that the Board or the Committee may, to the
extent it deems it necessary or desirable to comply with Section 162(m) of the
Code and applicable regulations thereunder, ensure that each Non-Employee
Director also qualifies as an outside director as that term is defined in the
regulations under Section 162(m) of the Code.

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          (q)  "Option(s)" shall mean an Incentive Stock Option or a non-
               ---------
               qualified stock option to purchase Shares that is awarded
               pursuant to the Plan.

          (r) "Option Agreement" shall mean a written agreement substantially in
               ----------------
the form of Exhibit A-1 or A-2, or such other form or forms as the Board or the
Committee (subject
to the terms and conditions of this Plan) may from time to time approve
evidencing and
reflecting the terms of an Option.

          (s) "Optionee" shall mean an Eligible Person to whom an Option is
               --------
awarded.

          (t) "Other Available Shares" means, as of any date, the excess, if any
               ----------------------
of:

               (i)  the total number of  Shares owned by an Optionee; over

               (ii) the sum of:

                    (A)  the number of Shares owned by such Optionee for less
                         than six months; plus

                    (B)  the number of Shares owned by such Optionee that has,
                         within the preceding six months, been surrendered as
                         payment in full or in part, of the exercise price for
                         an option to purchase any securities of the Company or
                         an Affiliate under any Company Plan.

          (u) "Participant" shall mean each Eligible Person of the Company or a
               -----------
Subsidiary to whom an Award is granted pursuant to the Plan.

          (v) "Person" shall mean an individual, partnership, corporation,
               ------
limited liability company, trust, joint venture, unincorporated association, or
other entity or association.

          (w) "Plan" shall mean the ViroPharma Incorporated Stock Option Plan,
               ----
as amended from time to time.

          (x) "Pool" shall mean the pool of Shares subject to the Plan, as
               ----
described in Section 6, and as adjusted in accordance with Section 9 of the
Plan.

          (y) "Securities Act" shall mean the Securities Act of 1933, as
               --------------
amended.

          (z) "Shares" shall mean shares of Common Stock.
               ------

          (aa) "Subsidiary" shall mean a subsidiary corporation, whether now or
                ----------
hereafter existing, as defined in Sections 424(f) and (g) of the Code.

          Section  3.  Participation.
                       -------------

          Participants in the Plan shall be selected by the Board or the
Committee from the Eligible Persons.  The Board or the Committee may make Awards
at any time and from time to

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time to Eligible Persons. Any Award may include or exclude any Eligible Person,
as the Board or the Committee shall determine in its sole discretion.


          Section 4.  Administration.
                      --------------

          (a) Procedure.  The Plan shall be administered by the Board.  The
              ---------
Board may at any time appoint a Committee consisting of not less than two
persons to administer the Plan on behalf of the Board, each of whom is a Non-
Employee Director, subject to such terms and conditions as the Board may
prescribe.  Members of the Committee shall serve for such period of time as the
Board may determine.  Members of the Board or the Committee who are eligible for
Options or have been awarded Options may vote on any matters affecting the
administration of the Plan or the award of any Options pursuant to the Plan,
except that no such member shall act upon the award of an Option to himself or
herself, but any such member may be counted in determining the existence of a
quorum at any meeting of the Board or the Committee during which action is taken
with respect to the award of Options to himself or herself.

          From time to time the Board may increase the size of the Committee and
appoint additional members thereto, remove members (with or without cause) and
appoint new members in substitution therefor, fill vacancies however caused, or
remove all members of the Committee and thereafter directly administer the Plan.

          (b) Powers of the Board and the Committee.  Subject to the provisions
              -------------------------------------
of the Plan, the Board or the Committee shall have the authority, in its
discretion:

              (i)   to make Awards;

              (ii)  to determine the Fair Market Value Per Share;

              (iii) to determine the exercise price of the Options to be awarded
                    in accordance with Section 7 of the Plan;

              (iv)  to determine the Eligible Persons to whom, and the time or
                    times at which, Awards shall be made, and the number of
                    Shares to be subject to each Award;

              (v)   to prescribe, amend and rescind rules and regulations
                    relating to the Plan;

              (vi)  to determine the terms and provisions of each Award under
                    the Plan and each Option Agreement (which need not be
                    identical with the terms of other Awards and Option
                    Agreements) and, with the consent of the Optionee, to modify
                    or amend an outstanding Award or Option Agreement;

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              (vii)  to determine the conditions which must be satisfied in
                     order for an Award to vest and become exercisable, which
                     conditions may include satisfaction of performance goals,
                     vesting over time, and other criteria as determined by the
                     Board or the Committee;

              (viii) to accelerate the vesting or exercise date of any Award;

              (ix)   to interpret the Plan or any agreement entered into with
                     respect to an Award or exercise of Options;

              (x)    to authorize any person to execute on behalf of the Company
                     any instrument required to effectuate an Award or to take
                     such other actions as may be necessary or appropriate with
                     respect to the Company's rights pursuant to Awards or
                     agreements relating to the Award or exercise thereof; and

              (xi)   to make such other determinations and establish such other
                     procedures as it deems necessary or advisable for the
                     administration of the Plan.

          (c) Effect of Decisions.  All decisions, determinations and
              -------------------
interpretations of the Board or the Committee shall be final and binding with
respect to all Awards under the Plan.

          (d) Limitation of Liability.  Notwithstanding anything herein to the
              -----------------------
contrary, no member of the Board or the Committee shall be liable for any good
faith determination, act or failure to act in connection with the Plan or any
Award hereunder.

          Section 5.  Eligibility.  Awards may be made only to Eligible Persons.
                      -----------
An Eligible Person who has received an Award, if he or she is otherwise
eligible, may receive additional Awards.

          Section 6.  Stock Subject to the Plan.    Subject to the provisions of
                      -------------------------
this Section 6 and the provisions of Section 9 of the Plan, the maximum
aggregate number of Shares which may be awarded and sold under the Plan is
2,750,000 Shares of Common Stock (collectively, the "Pool"). The maximum
aggregate number of Shares which may be awarded and sold under the Plan to any
individual Optionee is 500,000 Shares of Common Stock. Options awarded from the
Pool may be either Incentive Stock Options or non-qualified stock options, as
determined by the Board or the Committee. If an Option should expire or become
unexercisable for any reason without having been exercised in full, the Shares
which were subject thereto shall, unless the Plan shall have been terminated, be
returned to the Pool and become available for future award under the Plan.

          Section 7.  Terms and Conditions of Options.
                      -------------------------------

          Each Option awarded pursuant to the Plan shall be authorized by the
Board or the Committee and shall be evidenced by an Option Agreement in such
form as the Board or the Committee may from time to time determine.  Each Option
Agreement shall incorporate by reference all other terms and conditions of the
Plan, including the following terms and

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<PAGE>

conditions:

          (a) Number of Shares.  The number of Shares subject to the Option,
              ----------------
which shall not include fractional Shares.

          (b) Option Price.  The price per Share payable on the exercise of any
              ------------
Option  shall be stated in the Option Agreement and shall be no less than the
Fair Market Value Per Share of the Common Stock on the date such Option is
awarded, without regard to any restriction other than a restriction which will
never lapse.  Notwithstanding the foregoing, if an Option which is an Incentive
Stock Option shall be awarded under this Plan to any person who, at the time of
the award of such Option, owns stock possessing more than 10% of the total
combined voting power of all classes of the Company's stock, the price per Share
payable upon exercise of such Incentive Stock Option shall be no less than 110
percent (110%) of the Fair Market Value Per Share of the Common Stock on the
date such Option is awarded.   Neither the Board nor the Committee may reprice
any outstanding Options.

          (c) Consideration.  The consideration to be paid for the Shares to be
              -------------
issued upon the exercise of an Option, including the method of payment, shall be
determined by the Board or the Committee and may consist entirely of cash,
personal or certified check, or, at the election of the Optionee and as the
Board or the Committee may, in its sole discretion, approve, by surrendering
Shares with an aggregate Fair Market Value per Share equal to the aggregate
Option price, or by delivering such combination of Shares and cash as the Board
or the Committee may, in its sole discretion, approve; provided, however, that
                                                       -----------------
Shares may be surrendered in satisfaction of the Option price only if the
Optionee certifies in writing to the Company that the Optionee owns a number of
Other Available Shares as of the date the Option is exercised that is at least
equal to the number of  Shares to be surrendered in satisfaction of the Option
price; provided further, that the Option price may not be paid in Shares if the
       ----------------
Board or the Committee determines that such method of payment would result in
liability under Section 16(b) of the Exchange Act to an Optionee.

          Except as otherwise provided by the Board or the Committee, if payment
is made in whole or in part in Shares, the Optionee shall deliver to the Company
certificates registered in the name of such Optionee representing Shares legally
and beneficially owned by such Optionee, free of all liens, claims and
encumbrances of every kind and having an aggregate Fair Market Value on the date
of delivery that is not greater than the aggregate Option price accompanied by
stock powers duly endorsed in blank by the record holder of the Shares
represented by such certificates. If the Board or the Committee, in its sole
discretion, should refuse to accept Shares in payment of the Option price, any
certificates representing Shares which were delivered to the Company shall be
returned to the Optionee with notice of the refusal of the Board or the
Committee to accept such Shares in payment of the option price. The Board or the
Committee may impose such limitations and prohibitions on the use of Shares to
exercise an Option as it deems appropriate.

          (d) Form of Option.  The Option Agreement will state whether the
              --------------
Option awarded is an Incentive Stock Option or a non-qualified stock option, and
will constitute a binding determination as to the form of Option awarded.

                                       7
<PAGE>

          (e) Exercise of Options.  Any Option awarded hereunder shall be
              -------------------
exercisable at such times and under such conditions as shall be set forth in the
Option Agreement (as may be determined by the Board or the Committee and as
shall be permissible under the terms of the Plan), which may include performance
criteria with respect to the Company and/or the Optionee, and as shall be
permissible under the terms of the Plan.

          An Option may be exercised in accordance with the provisions of this
Plan as to all or any portion of the Shares then exercisable under an Option
from time to time during
the term of the Option.  If an Option is exercised for a fraction of a Share,
the Fair Market Value of such fractional Share, as of the date of exercise, will
be paid in cash.

          An Option shall be deemed to be exercised when written notice of such
exercise has been given to the Company at its principal executive office in
accordance with the terms of the Option Agreement by the person entitled to
exercise the Option and full payment for the Shares with respect to which the
Option is exercised has been received by the Company, accompanied by any
agreements required by the terms of the Plan and/or Option Agreement.  Full
payment may consist of such consideration and method of payment allowable under
this Section 7 of the Plan.  No adjustment shall be made for a dividend or other
right for which the record date is prior to the date the Option is exercised,
except as provided in Section 9 of the Plan.

          As soon as practicable after any proper exercise of an Option in
accordance with the provisions of the Plan, the Company shall, without transfer
or issue tax to the Optionee, deliver to the Optionee at the principal executive
office of the Company or such other place as shall be mutually agreed upon
between the Company and the Optionee, a certificate or certificates representing
the Shares for which the Option shall have been exercised.

          Exercise of an Option in any manner shall result in a decrease in the
number of Shares which thereafter may be available for sale under the Option by
the number of Shares as to which the Option is exercised.

          (f)  Term and Vesting of Options.
               ---------------------------

               (i)  Except as provided in Section 7(g)(iv), Options awarded
                    hereunder shall vest and become exercisable in whole or in
                    part, in accordance with such vesting conditions as the
                    Board or the Committee shall determine, which conditions
                    shall be stated in the Option Agreement. Options may be
                    exercised in any order elected by the Optionee whether or
                    not the Optionee holds any unexercised Options under this
                    Plan or any other plan of the Company.

               (ii) Notwithstanding any other provision of this Plan, no Option
                    shall be (A) awarded under this Plan after ten (10) years
                    from the date on which this Plan is adopted by the Board, or
                    (B) exercisable more than ten (10) years from the date of
                    award; provided, however, that if an Option that is intended
                           --------  -------
                    to be an Incentive Stock Option shall be awarded under this
                    Plan to any person who, at the time of the award of such
                    Option, owns stock possessing more than

                                       8
<PAGE>

                    10% of the total combined voting power for all classes of
                    the Company's stock, the foregoing clause (B) shall be
                    deemed modified by substituting "five (5) years" for the
                    term "ten (10) years" that appears therein.

             (iii)  No Option awarded to any Optionee shall be treated as an
                    Incentive Stock Option, to the extent such Option would
                    cause the aggregate Fair Market Value Per Share (determined
                    as of the date of award of each such Option) of the Shares
                    with respect to which Incentive Stock Options are
                    exercisable by such Optionee for the first time during any
                    calendar year to exceed $100,000. For purposes of
                    determining whether an Incentive Stock Option would cause
                    such aggregate Fair Market Value Per Share to exceed the
                    $100,000 limitation, such Incentive Stock Options shall be
                    taken into account in the order awarded.  For purposes of
                    this subsection, Incentive Stock Options include all
                    Incentive Stock Options under all plans of the Company that
                    are Incentive Stock Option plans within the meaning of
                    Section 422 of the Code.

        (g)  Termination of Options.
             ----------------------

             (i)  Unless sooner terminated as provided in this Plan, each
                  Option shall be exercisable for such period of time as shall
                  be determined by the Board or the Committee and set forth in
                  the Option Agreement, and shall be void and unexercisable
                  thereafter.

             (ii) Except as otherwise provided herein or by the terms of any
                  Award, with respect to an Optionee who is an employee or
                  Director, upon the termination of such Optionee's employment
                  or other relationship with the Company for any reason, Options
                  exercisable on the date of such termination shall be
                  exercisable by the Optionee (or in the case of the Optionee's
                  death subsequent to termination of employment or such other
                  relationship, by the Optionee's executor(s) or
                  administrator(s)) for a period of three (3) months from the
                  date of the Optionee's termination.

                  Except as otherwise provided herein or by the terms of any
                  Award, with respect to an Optionee who is an advisor or
                  consultant, the termination of such Optionee's relationship
                  with the Company for any reason shall not accelerate the
                  expiration date of Options exercisable on the date of
                  termination; provided however, that if such Optionee dies
                               ----------------
                  following such termination, the Option shall be exercisable
                  for a period of twelve (12) months commencing on the date of
                  the Optionee's death by such Optionee's executor(s) or
                  administrator(s).

                                       9
<PAGE>

          (iii)  Except as otherwise provided herein or by the terms of any
                 Award, upon the Disability or death of an Optionee while in the
                 service of the Company, Options held by such Optionee which are
                 exercisable on the date of Disability or death shall be
                 exercisable for a period of twelve (12) months commencing on
                 the date of the Optionee's Disability or death, by the Optionee
                 or his legal guardian or representative or, in the case of
                 death, by his executor(s) or administrator(s).

          (iv)   Options may be terminated at any time by agreement between the
                 Company and the Optionee.



     (h)  Forfeiture.
          ----------

          (i) Termination for Cause.  Notwithstanding any other provision of
              ---------------------
this Plan, if the Optionee's employment or engagement is terminated by the
Company, and the Board or the Committee makes a determination that the Optionee:

              (A)  has engaged in any type of disloyalty to the Company,
                   including without limitation, fraud, embezzlement,
                   theft, or dishonesty in the course of his employment or
                   engagement, or has otherwise breached any fiduciary
                   duty owed to the Company;

              (B)  has been convicted of a felony;

              (C)  has disclosed trade secrets or confidential information
                   of the Company; or

              (D)  has breached any agreement with or duty to the Company
                   in respect of confidentiality, non-disclosure, non-
                   competition or otherwise,

then all unexercised Options shall terminate upon the date of such a finding,
or, if earlier, the date of termination of employment or engagement for such a
finding, and the Optionee shall forfeit all Shares for which the Company has not
yet delivered share certificates to the Optionee and the Company shall refund to
the Optionee the Option purchase price paid to it, if any, in the same form as
it was paid (or in cash at the Company's discretion).  Notwithstanding anything
herein to the contrary, the Company may withhold delivery of share certificates
pending the resolution of any inquiry that could lead to a finding resulting in
forfeiture.

          (ii) Non-Competition.  Notwithstanding any other provision of this
               ---------------
Plan, if, during the 3-month period following a termination of service, which
period shall be extended to 12 months in the event of a termination due to
Disability, an Optionee who is not a consultant or advisor commences any
employment or engagement with or by a competitor of the Company (including, but
not limited to, full or part-time employment or independent consulting

                                       10
<PAGE>

work), as determined in the sole discretion of the Board or the Committee, all
unexercised Options shall terminate immediately upon the commencement thereof.
In the event an Optionee who is a consultant or advisor has entered into an
agreement with the Company which contains non-competition covenants and such
consultant or advisor violates the terms of his or her non-competition covenant,
all unexercised Options shall terminate immediately upon the date of such
violation.

          Section 8.  Determination of Fair Market Value Per Share of Common
                      ------------------------------------------------------
     Stock.
     ------

          (a) Except to the extent otherwise provided in this Section 8, the
Fair Market Value Per Share of Common Stock shall be determined by the Board or
the Committee in its sole discretion.

          (b) Notwithstanding the provisions of Section 8(a), in the event that
shares of Common Stock are traded in the over-the-counter market, the Fair
Market Value Per Share of Common Stock shall be the mean of the bid and asked
prices for a share of Common Stock on the relevant valuation date as reported in
The Wall Street Journal (or, if not so reported, as otherwise reported by the
-----------------------
National Association of Securities Dealers Automated Quotations ("NASDAQ")
System), as applicable or, if there is no trading on such date, on the next
preceding date on which there were reported share prices.  In the event shares
of Common Stock are listed on a national or regional securities exchange or
traded through the NASDAQ National Market, the Fair Market Value of a share of
Common Stock shall be the closing price for a share of Common Stock on the
exchange or on the NASDAQ National Market, as reported in The Wall Street
                                                          -------- ------
Journal on the relevant valuation date, or if there is no trading on that date,
-------
on the next preceding date on which there were reported share prices.

          Section 9.  Adjustments.
                      -----------

          (a) Subject to required action by the stockholders, if any, the number
of Shares as to which Awards may be made under this Plan, including the
individual limit specified in Section 6, and the number of Shares subject to
outstanding Options and the Option prices thereof shall be adjusted
proportionately for any increase or decrease in the number of outstanding Shares
of Common Stock of the Company resulting from stock splits, reverse stock
splits, stock dividends, reclassifications and recapitalizations, merger,
consolidation, exchange of shares, or any similar change affecting Common Stock.

          (b) No fractional Shares shall be issuable on account of any action
mentioned in Section 9(a), and the aggregate number of Shares into which Shares
then covered by the Award, when changed as the result of such action, shall be
increased to the next highest whole number of Shares resulting from such action,
provided that no such increase shall be made if such increase would cause an
Incentive Stock Option to lose its status as such without the consent of the
Optionee.

          Section 10.  Rights as a Stockholder.
                       -----------------------

          A recipient of an Award shall have no rights as a stockholder of the
Company and shall neither have the right to vote nor receive dividends with
respect to any Shares subject

                                       11
<PAGE>

to an Option until such Option has been exercised and a certificate with respect
to the Shares purchased upon such exercise has been issued to him.

          Section 11.  Time of Awarding Options.
                       ------------------------

          The date of an Award shall, for all purposes, be the date which the
Board or the Committee specifies when the Board or the Committee makes its
determination that an Award is made, or if none is specified, then the date of
such determination.  Notice of the determination shall be given to each Eligible
Person to whom an Award is made within a reasonable time after the date of such
Award.

          Section 12.  Modification, Extension and Renewal of Option.
                       ---------------------------------------------

          Subject to the terms and conditions of the Plan, the Board or the
Committee may modify, extend or renew an Award, or accept the surrender of an
Award (to the extent not theretofore exercised).  Notwithstanding the foregoing,
(a) no modification of an Award which adversely affects the Optionee shall be
made without the consent of the Optionee, and (b) no Incentive Stock Option may
be modified, extended or renewed if such action would cause it to cease to be an
"Incentive Stock Option" within the meaning of Section 422 of the Code, unless
the Optionee specifically acknowledges and consents to the tax consequences of
such action.

          Section 13.  Purchase for Investment and Other Restrictions.
                       ----------------------------------------------

          (a) The obligation of the Company to issue Shares to an Optionee upon
the exercise of an Option granted under the Plan is conditioned upon such
issuance complying with all relevant provisions of applicable law, including,
without limitation, the Securities Act, the Exchange Act, the rules and
regulations promulgated thereunder and any applicable foreign laws.

          (b) At the option of the Board or the Committee, the obligation of the
Company to issue Shares to an Optionee upon the exercise of an Option granted
under the Plan may be conditioned upon obtaining appropriate representations,
warranties, restrictions and agreements of the Optionee.  Among other
representations, warranties, restrictions and agreements, the Optionee may be
required to represent and agree that the purchase of Shares shall be for
investment, and not with a view to the public resale or distribution thereof,
unless the Shares are registered under the Securities Act and the issuance and
sale of the Shares complies with all other laws, rules and regulations
applicable thereto.  Unless the issuance of such Shares is registered under the
Securities Act (and any similar law of a foreign jurisdiction applicable to the
Optionee), the Optionee shall acknowledge that the Shares purchased are not
registered under the Securities Act (or any such other law) and may not be sold
or otherwise transferred unless the Shares have been registered under the
Securities Act (or any such other law) in connection with the sale or other
transfer thereof, or that counsel satisfactory to the Company has issued an
opinion satisfactory to the Company that the sale or other transfer of such
Shares is exempt from registration under the Securities Act (or any such other
law), and unless said sale or transfer is in compliance with all other
applicable laws, rules and regulations, including all applicable federal, state
and foreign securities laws, rules and regulations.  Unless the Shares subject
to an Award are registered under the Securities Act, the certificates
representing such Shares issued shall contain the following legend in
substantially the following form:

                                       12
<PAGE>

          THE SHARES REPRESENTED BY THIS CERTIFICATE HAVE NOT BEEN REGISTERED
          UNDER THE SECURITIES ACT OF 1933, AS AMENDED OR ANY APPLICABLE STATE
          SECURITIES LAWS.  THESE SHARES HAVE NOT BEEN ACQUIRED WITH A VIEW TO
          DISTRIBUTION OR RESALE, AND MAY NOT BE SOLD, ASSIGNED, EXCHANGED,
          MORTGAGED, PLEDGED, HYPOTHECATED OR OTHERWISE TRANSFERRED OR DISPOSED
          OF, BY GIFT OR OTHERWISE, OR IN ANY WAY ENCUMBERED WITHOUT AN
          EFFECTIVE REGISTRATION STATEMENT FOR SUCH SHARES UNDER THE SECURITIES
          ACT OF 1933, AS AMENDED, AND ANY APPLICABLE STATE SECURITIES LAWS, OR
          A SATISFACTORY OPINION OF COUNSEL SATISFACTORY TO VIROPHARMA
          INCORPORATED THAT REGISTRATION IS NOT REQUIRED UNDER SUCH ACT AND
          UNDER APPLICABLE STATE SECURITIES LAWS.

If required under the laws of any jurisdiction in which the Optionee resides,
the certificate or certificates may bear any such legend.



          Section 14.  Transferability.
                       ---------------

          No Option shall be assignable or transferable otherwise than by will
or by the laws of descent and distribution.  During the lifetime of the
Optionee, his Options shall be exercisable only by such Optionee, or, in the
event of his or her legal incapacity or Disability, then by the Optionee's legal
guardian or representative.

          Section 15.  Other Provisions.
                       ----------------

          The Option Agreement may contain such other provisions as the Board or
the Committee in its discretion deems advisable and which are not inconsistent
with the provisions of this Plan, including, without limitation, restrictions
upon or conditions precedent to the exercise of the Option.

          Section 16.  Change of Control.
                       -----------------

          (a) Notwithstanding anything to the contrary set forth in this Plan,
in the event of a Change of Control in which the Plan is not continued by a
successor corporation, or in which equivalent, substituted options for common
stock in a successor corporation are not provided to Optionees, the Plan shall
be terminated and, with respect to Optionees who are employees of the Company or
any of its Subsidiaries or who are members of the Board, all unvested Options
shall vest as follows: (i) with respect to such Optionees who have been employed
by the Company or a Subsidiary or who have served on the Board for at least two
years as of the Change of Control, Options shall be fully and immediately vested
and exercisable; and (ii) with respect to all other such Optionees, fifty
percent (50%) of that portion of the Options which are not vested as of the date
of the Change of Control shall be immediately vested and exercisable and the
remaining portion of the Options which are not vested shall lapse and be
forfeited.

                                       13
<PAGE>

          (b) In the event of a Change of Control in which the Plan is continued
by a successor corporation or in which equivalent substituted options for common
stock in a successor corporation are provided to Optionees, with respect to
Optionees who are employees of the Company or any of its Subsidiaries or who are
members of the Board, Options shall vest as follows:  (i) if an Optionee who is
employed by the Company and serves on the Company's management team (each, an
"Executive Officer") or is a member of the Board at the time of the Change of
Control is not offered substantially equivalent employment with the successor
corporation or a related employer (both in terms of duties and compensation),
then any unvested Options as of the date of the Change of Control held by such
Executive Officer or member of the Board shall be fully and immediately vested
and exercisable in accordance with Section 16(a)(i) or 16(a)(ii), as applicable,
taking into account all service performed with the Company in any capacity for
purposes of vesting; and (ii) if any Optionee is offered substantially
equivalent employment with the successor corporation or a related employer (both
in terms of duties and compensation), then Options shall not be subject to
accelerated vesting; provided however, that if the Optionee's employment with
the successor corporation or related employer is terminated by the successor
corporation or related employer during the six month period following such
Change of Control, then any unvested Options or substituted options shall be
fully and immediately vested and exercisable at the date of the Optionee's
termination of employment in accordance with Section 16(a)(i) or 16(a)(ii), as
applicable, taking  into account service performed with the Company and the
successor corporation and all related employers for purpose of vesting.

          (c) Notwithstanding Sections 16(a) and (b) hereof, any Optionee who is
a "disqualified individual", as that term is defined in Section 280G(c) of the
Code, shall be notified by the Committee of any event which may constitute a
Change of Control in advance of the effective date of such Change of Control.
Notice shall be provided, in the sole discretion of the Committee, as soon as
reasonably practicable prior to the Change of Control. The disqualified
individual may refuse to accept accelerated vesting of his or her Options after
consideration of the tax consequences to such disqualified individual resulting
from the Change of Control, provided that any such refusal shall be communicated
to the Committee in writing prior to the Change of Control. If it is not
practicable to provide advance notice of such Change of Control, the
disqualified individual will be deemed to have elected to refuse such
acceleration, but only to the extent that it is determined, as soon as
practicable after the Change of Control, that accelerated vesting will result in
negative tax consequences under Section 280G of the Code.

          (d) In addition to arranging for the exchange of Options for options
to purchase common stock in a successor corporation, in the event of a Change of
Control of the Company by reason of a merger, consolidation or tax free
reorganization or sale of all or substantially all of the assets of the Company,
the Board shall have the authority, in its discretion, to terminate this Plan
and to distribute to each Optionee cash and/or other property in an amount equal
to and in the same form as the Optionee would have received from the successor
corporation if the Optionee had owned the Shares subject to the Option rather
than the Option at the time of the Change of Control, provided that any such
amount paid to an Optionee shall reflect the deduction of the exercise price the
Optionee would have paid to purchase such

                                       14
<PAGE>

Shares. The form of payment or distribution to the Optionee pursuant to this
Section shall be determined by the Committee.

          Section 17.  Amendment of the Plan.
                       ---------------------

          Insofar as permitted by law and the Plan, and subject to Section
20(c), the Board or the Committee may from time to time suspend, terminate or
discontinue the Plan or revise or amend it in any respect whatsoever with
respect to any Shares at the time not subject to an Option, including amendments
necessary or advisable to assure that the Incentive Stock Options or the non-
qualified stock options available under the Plan continue to be treated as such,
respectively, under all applicable laws.

          Section 18.  Application of Funds.
                       --------------------

          The proceeds received by the Company from the sale of Shares pursuant
to the exercise of Options shall be used for general corporate purposes or such
other purpose as may be determined by the Board.

          Section 19.  No Obligation to Exercise Option.
                       --------------------------------

          The awarding of an Option shall impose no obligation upon the Optionee
to exercise such Option.



          Section 20.  Approval of Stockholders.
                       ------------------------

          (a) Effective Date of Plan.  This amendment and restatement of the
              ----------------------
Plan shall become effective on the date that it is adopted by the Board;

provided, however, that this amendment and restatement shall be rescinded, and
-----------------
all actions taken pursuant to the Plan, as amended and restated (except the
granting of Options with respect to Shares initially authorized

for award under the Plan prior this amendment and restatement), shall be null
and void as of the first anniversary of the date of adoption by the Board
unless, before such first anniversary, the Plan, as amended and restated, is
approved by a majority of the votes cast at a duly held stockholder meeting at
which a quorum representing a majority of the Company's outstanding voting
shares is present, either in person or by proxy.

          (b) Awards Prior to Stockholder Approval.  The Board or the Committee
              ------------------------------------
may make Awards hereunder before the stockholder meeting at which the Plan, as
amended and restated, will be presented to the Company's stockholders for
approval; provided, however, that any and all Options awarded for Shares in
          -----------------
excess of 2,000,000 Shares, the number of Shares initially authorized for award
under the Plan prior to this amendment and restatement, shall lapse
automatically on the first anniversary of the date of adoption by the Board if
the Plan is not approved by such stockholders on or before such date. With
respect to Options awarded before the earlier of the date the Plan is approved
by the Company's stockholders or the first

                                       15
<PAGE>

anniversary of the date the Plan is adopted by the Board, the Board or the
Committee shall designate whether the Option is for Shares previously authorized
for award under the Plan, or is for Shares as to which stockholder approval is
pending.

         (c) Stockholder Approval of  Certain Amendments.
             -------------------------------------------

             (i)   If the Board or the Committee amends the Plan to increase the
                   aggregate number of Shares for which Options may be awarded
                   hereunder, and approval of the stockholders by a majority of
                   the votes cast at a duly held stockholder meeting at which a
                   quorum representing a majority of the Company's outstanding
                   voting shares is present (either in person or by proxy), is
                   not obtained within twelve (12) months of the adoption of
                   such amendment, all Options awarded with respect to such
                   increased number of shares shall lapse automatically on the
                   first anniversary of the date of the adoption of such
                   amendment.

             (ii)  If the Board or the Committee amends the Plan to change the
                   designation of the class of employees eligible to receive
                   Options, and approval of the stockholders by a majority of
                   the votes cast at a duly held stockholder meeting at which a
                   quorum representing a majority of the Company's outstanding
                   voting shares is present (either in person or by proxy), is
                   not obtained within twelve (12) months of the adoption of
                   such amendment, all Incentive Stock Options awarded after the
                   date of such adoption automatically shall be converted into
                   non-qualified stock options on the first anniversary of the
                   date of the adoption of such amendment.

             (iii) Section 7(b) of the Plan may not be amended to permit the
grant of Options with an exercise price below Fair Market Value or to permit
outstanding Options to be repriced unless such amendment is approved by the
stockholders by a majority of the votes cast at a duly held stockholder meeting
at which a quorum representing a majority of the Company's outstanding voting
shares is present (either in person or by proxy).

         Section 21.  Conditions Upon Issuance of Shares.
                      ----------------------------------

         Shares shall not be issued pursuant to the exercise of an Option unless
the exercise of such Option and the issuance and delivery of such Shares
pursuant thereto shall comply with all relevant provisions of law, including,
without limitation, the Securities Act, the Exchange Act, the rules and
regulations promulgated thereunder, and the requirements of any stock exchange
upon which the Shares may then be listed, and shall be further subject to the
approval of counsel for the Company with respect to such compliance.

         Section 22.  Reservation of Shares.
                      ---------------------

                                       16
<PAGE>

          The Company, during the term of this Plan, shall at all times reserve
and keep available such number of Shares as shall be sufficient to satisfy the
requirements of the Plan.

          The Company, during the term of this Plan, shall use its best efforts
to seek to obtain from appropriate regulatory agencies any requisite
authorization in order to issue and sell such number of Shares as shall be
sufficient to satisfy the requirements of the Plan.  The inability of the
Company to obtain from any such regulatory agency having jurisdiction the
requisite authorization(s) deemed by the Company's counsel to be necessary for
the lawful issuance and sale of any Shares hereunder, or the inability of the
Company to confirm to its satisfaction that any issuance and sale of any Shares
hereunder will meet applicable legal requirements, shall relieve the Company of
any liability in respect to the failure to issue or sell such Shares as to which
such requisite authority shall not have been obtained.

          Section 23.  Stock Option Agreements.
                       -----------------------

          Options shall be evidenced by an Option Agreement in such form or
forms as the Board or the Committee shall approve from time to time.

          Section 24.  Taxes, Fees, Expenses and Withholding of Taxes.
                       ----------------------------------------------

          (a) The Company shall pay all original issue and transfer taxes (but
not income taxes, if any) with respect to the award of Options and/or the issue
and transfer of Shares pursuant to the exercise thereof, and all other fees and
expenses necessarily incurred by the Company in connection therewith, and will
use its best efforts to comply with all laws and regulations which, in the
opinion of counsel for the Company, shall be applicable thereto.

          (b) The award of Options hereunder and the issuance of Shares pursuant
to the exercise of Options is conditioned upon the Company's reservation of the
right to withhold in accordance with any applicable law, from any compensation
or other amounts payable to the Optionee, any taxes required to be withheld
under federal, state or local law as a result of the award or exercise of such
Option or the sale of the Shares issued upon exercise thereof.  To the extent
that compensation or other amounts, if any, payable to the Optionee is
insufficient to pay any taxes required to be so withheld, the Company may, in
its sole discretion, require the Optionee (or such other person entitled herein
to exercise the Option), as a condition of the exercise of an Option, to pay in
cash to the Company an amount sufficient to cover such tax liability or
otherwise to make adequate provision for the Company's satisfaction of its
withholding obligations under federal, state and local law, provided that such
satisfaction of tax liability is made within 60 days of the date on which
written notice of exercise has been given to the Company.

          Section 25.  Notices.
                       -------

          Any notice to be given to the Company pursuant to the provisions of
this Plan shall be addressed to the Company in care of its Secretary (or such
other person as the Company may designate from time to time) at its principal
executive office, and any notice to be given to an Optionee shall be delivered
personally or addressed to him or her at the address given beneath his or her
signature on his or her Option Agreement, or at such other address as such
Optionee or his or her permitted transferee (upon the transfer of the Shares)
may hereafter designate in

                                       17
<PAGE>

writing to the Company. Any such notice shall be deemed duly given on the date
and at the time delivered via hand delivery, courier or recognized overnight
delivery service or, if sent via telecopier, on the date and at the time
telecopied with confirmation of delivery or, if mailed, on the date five (5)
days after the date of the mailing (which shall be by regular, registered or
certified mail). Delivery of a notice by telecopy (with confirmation) shall be
permitted and shall be considered delivery of a notice notwithstanding that it
is not an original that is received. It shall be the obligation of each Optionee
and each permitted transferee holding Shares purchased upon exercise of an
Option to provide the Secretary of the Company, by letter mailed as provided
herein, with written notice of his or her direct mailing address.

          Section 26.  No Enlargement of Optionee Rights.
                       ---------------------------------

          This Plan is purely voluntary on the part of the Company, and the
continuance of the Plan shall not be deemed to constitute a contract between the
Company and any Optionee, or to be consideration for or a condition of the
employment or service of any Optionee.  Nothing contained in this Plan shall be
deemed to give any Optionee the right to be retained in the employ or service of
the Company or any Subsidiary, or to interfere with the right of the Company or
any such corporation to discharge or retire any Optionee thereof at any time
subject to applicable law.  No Optionee shall have any right to or interest in
Awards authorized hereunder prior to the award thereof to such Optionee, and
upon such Award he shall have only such rights and interests as are expressly
provided herein, subject, however, to all applicable provisions of the Company's
Certificate of Incorporation, as the same may be amended from time to time.

          Section 27.  Information to Optionees.
                       ------------------------

          The Company, upon request, shall provide without charge to each
Optionee copies of such annual and periodic reports as are provided by the
Company to its stockholders generally.



          Section 28.  Availability of Plan.
                       --------------------

          A copy of this Plan shall be delivered to the Secretary of the Company
and shall be shown by him to any eligible person making reasonable inquiry
concerning it.

          Section 29.  Invalid Provisions.
                       ------------------

          In the event that any provision of this Plan is found to be invalid or
otherwise unenforceable under any applicable law, such invalidity or
unenforceability shall not be construed as rendering any other provisions
contained herein as invalid or unenforceable, and all such other provisions
shall be given full force and effect to the same extent as though the invalid or
unenforceable provision was not contained herein.

          Section 30.  Applicable Law.
                       --------------

          This Plan shall be governed by and construed in accordance with the
laws of the Commonwealth of Pennsylvania.

                                       18
<PAGE>

          Executed this 13th day of March, 2000.


[CORPORATE SEAL]                        VIROPHARMA INCORPORATED


Attest: _________________________       By:_______________________________

                                       19