6 In the wake of current pandemic of COVID-19, there has aris en an urgent need to come up 7 with novel ways to detect the infected person with SARS-CoV- 2 at an extremely fast pace so 8 that the person is immediately quarantined to prevent furthe r transmission of the virus to 9 other susceptible individuals. Such quick detection measures would allow the timely 10 mitigation of the dreadful disease which has claimed close t o 100,000 lives worldwide. In this 11 article, a very fast and cheap way to detect the presen ce of SARS-CoV in the biopsied tissue 12 has been proposed. The current method discussed here would drasti cally reduce the time of 13 detection of an infected person to less than ~ 6 hours in addit ion to the economic benefit of 14 using paper-based isoelectric focusing. The infecting coronavirus that causes severe 15 respiratory distress contains four major types of structural prote ins: spike (S) proteins, 16 membrane (M) proteins, envelope (E) proteins & nucleocapsid (N) proteins. Peculiar 17 isoelectric points of these four structural proteins have been propos ed to detect the SARS- 18 CoV infection. This work would be of immense interest to the sci entists, researchers as well 19 as health professionals who are trying to mitigate the spread of the disease as well as to cure 20 it at the same time. 21 Introduction 22 With the spread of the fatal COVID-19 that has become a pandemic, researchers worldwide 23 are trying to accelerate the detection as well as trea tment regimens of the zoonotic 24 coronavirus-related disease. The disease is caused by a fam ily of virus, known as 25 Coronavirus , causing the acute respiratory distress in the patients. Thus, the disease that is 26 caused by such virus is known as Severe Acute Respiratory Syndrome abbreviated as SARS . 27 This virus is known to contain four major structural proteins, spike (S) proteins, membrane 28 (M) proteins, envelope (E) proteins & nucleocapsid (N) proteins th at are spatially arranged 29 and distributed within the spherical virus particle, as shown in the schematic in Fig. 1. 30 31 Fig. 1 Schematic diagram of the SARS-CoV is shown, depicting the spatial arrangement of 32 various structural proteins [1]. 33 The pathogenicity of the virus depends on its attachment with the hum an angiotensin- 34 converting-enzyme-2 (ACE-2) via S-protein. Thus, the S-protein ha s garnered great attention 35 of the scientific community to deter the infection and to find its cure [2]. The four major 36 structural proteins namely, S, E, M & N of the SARS-CoV hav e distinct isoelectric points 37 (pI ) ranging from acidic to basic pH ranges, as shown in Table-1 . 38 Structural protein of SARS-CoV Isoelectric point ( pI ) Spike (S) 5.4 Envelope (E) 6.3 Membrane (M) 9.8 Nucleocapsid (N) 10.5 Table 1 Isoelectric points ( pI ) of major structural proteins of SARS-CoV are shown, 39 depicting a spike in pI values of M & N proteins in the alkaline range [3]. 40 Currently, the detection of infected person is done by the FD A approved RT-PCR test that 41 requires specialized costly instruments to perform polymeras e chain reaction (PCR) using a 42 reverse transcriptase (RT) and specific DNA primers to de tect the RNA from infecting 43 coronavirus [4]. In this article, the concept of paper-based i soelectric focusing is proposed to 44 identify the presence of SARS-CoV infection in the sample usi ng the isoelectric points of M 45 & N structural proteins that fall in the alkaline range ( pI values: 9.8 & 10.5). Such choice of 46 proteins to detect SARS-CoV is made because all the other proteins present in the extracted 47 sample from the patient would not normally have as high isoele ctric points as that of 48 structural proteins M & N. Nearly 10-15% proteomes from the non-redu ndant NCBI protein 49 database (having 86 million proteins) & ~5% proteomes from the UniProtKB/TrEMBL 50 protein database (having 63 million proteins) have pI values ~10 [5]. Viral characterizations 51 have been reported earlier by the analyses of capsid proteins [6, 7]. Here, a very fast and 52 economically viable way to detect the infection of the sa mple with SARS-CoV has been 53 proposed which would pave the way to reduce the detection timespa n that could be used in 54 low-cost settings in developing countries. 55 Methodology 56 Virus purification from cell lysate [8] 57 • Sample containing the virus would be subjected to hypotonic burst using 5 ml of 58 double distilled water following 15 minutes incubation at room tempe rature. The cell 59 debris would be separated from the infecting virus particles by centrifuging the lysate 60 at 3000×g for 15 minutes. The resulting supernatant would be containing the virus 61 particles that would further be removed by pipeting and mixing w ith equal volumes of 62 2× DMEM containing 4% FCS, 2% penicillin-streptomycin solution, and 4 mM L- 63 glutamine for restoration of the tonicity as in case of the original virus stock. 64 • Alternatively, viruses can also be collected from the brea th samples of the suspected 65 individuals infected with coronavirus [9]. The virus samples could be collected using 66 simple breath-analyzer tools that are regularly used by law- enforcing agencies to 67 check drunk driving cases. 68 Separation of viral capsid proteins from viruses [10] 69 • Virus particles have been reported to degrade at pH 10.5. Using the mentioned 70 protocol in the reference therein, the viral capsid proteins would be separated for 71 further analytical procedures. 72 Paper-based isoelectric focusing [11] 73 • The setup for paper-based would be prepared using the materials & methods 74 described in the reference therein. The separation of viral capsid proteins would take 75 ~2 hours if the applied focusing voltage was kept at 500 V wher eas the time of pI - 76 based separation would get reduced to ~30 minutes upon application of focusing 77 voltage of 1500 V. The schematic diagram for such analytical pr ocedure is shown in 78 Fig. 2. 79 80 81 Fig. 2 Schematic diagram of the paper-based isoelectric focusing setup is shown. The time 82 taken for separation of viral capsid proteins would be close to ~1 hour, as discussed earlier. 83 Discussion 84 The above discussed method to analyze the sample collected from the diseased person for 85 SARS-CoV infection provides a novel way to detect such infect ions. This analytical tool is 86 extremely time-efficient (takes less than ~ 6 hours) and cost-effective in comparison to 87 currently employed techniques that require DNA polymerases, sp ecific DNA primers that 88 would complement the genetic sequence of the infecting virus. In the proposed method, the 89 viral capsid proteins could be detected just on the basis of their respective isoelectric points 90 with pI values of M & N structural proteins in the very peculiar r ange ( pI > 9). This range is 91 extremely uncommon in common histological samples, thus would becom e a unique 92 signature for the presence of SARS-CoV in the analyzed samp le. This work would be of 93 immense interest to the scientists, researchers as wel l as health professionals who are working 94 towards the mitigation of the dreadful respiratory viruses, especially in the wake of current 95 pandemic COVID-19. 96