Vírusellenes terápiás lehetőségek COVID–19 fertőzés kezelésére
Authors: Keserű György Miklós 
Published: October 2021

Összefoglaló. A COVID–19-járvány egyre növekvő számú fertőzött
betegének ellátása érdekében rövid időn belül szükség mutatkozott vírusellenes
terápiás lehetőségekre. A gyors reagálás szempontját figyelembe véve erre a
célra elsősorban más vírusok ellen már kifejlesztett vírusellenes szerek
jöhetnek szóba. A magyar betegek ellátásbiztonsága szempontjából különösen
fontos a hatóanyagok és gyógyszerkészítmények hazai gyártása. Ezt a cél tűzte ki
a favipiravir, egy széles spektrumú antivirális hatóanyag hazai fejlesztése,
amely sikeresen befejeződött, a gyógyszerkészítmény klinikai vizsgálata
folyamatban van.

Summary. Increasing impact of COVID-19 on the healthcare system
prompted the identification of potential antiviral therapies. Due to the
immediate demand, known drugs were subjected to repositioning attempts. These
drugs include agents inhibiting the viral entry into the host cells, drugs
potentially blocking the release of the viral RNA from the endosomes, antivirals
inhibiting the replication of the viral RNA and finally compounds that might
prevent the assembly of the new virion. Since there is less experience with
camostat and nafamostat, the entry inhibitors tested in Japan, and due to the
ambiguous data collected with the endosome blocking chloroquine and
hydroxyl-chloroquine, we focused on the actual antiviral treatment options for
COVID-19 infections. In addition to favipiravir and remdesivir that were used
early, at the onset of the pandemic, we discuss novel candidates including
molnupiravir, a promising antiviral actually investigated in clinical trials.
Considering the needs of Hungarian COVID patients and the security of supply as
first priority, we selected favipiravir and developed a convenient process for
the industry-scale production of the active pharmaceutical ingredient (API). At
the end of this review we summarize the development and clinical investigation
of favipiravir, a wide spectrum antiviral drug used for the treatment of mild
and moderate COVID patients in Hungary in both ambulant and clinical settings.
The Hungarian COVID Task Force set up two consortia, one for the development and
the other for the clinical investigations of favipiravir. The objective of the
favipiravir development consortium was to develop processes for the production
of Favipiravir API and dosage forms. The consortium completed the pilot plant
scale industrial production of the API and produced clinical samples for the
upcoming trials. The selection and laboratory scale optimization of the
synthesis route was performed at the Medicinal Chemistry Research Group of the
Research Center for Natural Sciences. The laboratory scale synthesis was scaled
up for pilot plant production at EVI plc and Gedeon Richter plc. GMP production
was realized at the facilities of Gedeon Richter plc. Finished dosage forms were
developed at Meditop Ltd who produced the clinical samples under GMP conditions.
The clinical consortium is headed by the Hungarian section of the European
Clinical Research Infrastructure Network (ECRIN) and organized two trials. One
of these trials investigates favipiravir produced in Hungary while the other
trial is performed with favipiravir produced in Japan. Both studies were
approved by the Hungarian regulatory agency (OGYÉI) and are ongoing.