Potential drug targets of SARS-CoV-2: From genomics to therapeutics.

Affiliation

Shamsi A(1), Mohammad T(2), Anwar S(2), Amani S(3), Khan MS(4), Husain FM(5), Rehman MT(6), Islam A(2), Hassan MI(2).
Author information:
(1)Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India. Electronic address: [Email]
(2)Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
(3)Department of Biochemistry, F/O Life Science, Aligarh Muslim University, Aligarh, India.
(4)Department of Biochemistry, College of Sciences, King Saud University, Riyadh 11451, Saudi Arabia.
(5)Department of Food Science and Nutrition, Faculty of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Saudi Arabia.
(6)Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Abstract

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from China has become a global threat due to the continuous rise in cases of Coronavirus disease 2019 (COVID-19). The problem with COVID-19 therapeutics is due to complexity of the mechanism of the pathogenesis of this virus. In this review, an extensive analysis of genome architecture and mode of pathogenesis of SARS-CoV-2 with an emphasis on therapeutic approaches is performed. SARS-CoV-2 genome consists of a single, ~29.9 kb long RNA having significant sequence similarity to BAT-CoV, SARS-CoV and MERS-CoV genome. Two-third part of SARS-Cov-2 genome comprises of ORF (ORF1ab) resulting in the formation of 2 polyproteins, pp1a and pp1ab, later processed into 16 smaller non-structural proteins (NSPs). The four major structural proteins of SARS-CoV-2 are the spike surface glycoprotein (S), a small envelope (E), membrane (M), and nucleocapsid (N) proteins. S protein helps in receptor binding and membrane fusion and hence plays the most important role in the transmission of CoVs. Priming of S protein is done by serine 2 transmembrane protease and thus plays a key role in virus and host cell fusion. This review highlights the possible mechanism of action of SARS-CoV-2 to search for possible therapeutic options.