The number of global infections due to the novel coronavirus (SARS-CoV–2) reached over 22,262,946 infections with over 784,107 deaths on August 20, 2020. Stats are continuously changing (“Coronavirus (COVID–19) - Google News,” n.d.). The virus was initially transmitted to humans from other animals and then via person-to-person contact. It is not airborne, but aerosols and contact base transmission are the usual modes of transmission. The mechanism of the rapid transmission and why the same viral strain causes death in some persons and mild symptoms in others remain obscure. Coronavirus belongs to the subfamily Coronavirinae along with Torovirinae, and is grouped into the Coronaviridae family (Belouzard, Millet, Licitra, & Whittaker, 2012). Coronavirus (SARS-CoV–2) infections have recurred from time to time across various geographic regions. It is responsible for almost 30% of all respiratory infections in humans and other animals and causes great economic loss. Alpha and beta types of CoV mostly target human hosts, and other serological genera include beta, gamma and delta types (https://talk.ictvonline.org/taxonomy/). The RNA-based genome of CoV is the largest among known RNA viruses and it has high zoonotic potential for recombination and infecting new animal hosts including humans (Lai, Shih, Ko, Tang, & Hsueh, 2020). Viral sequences are under continuous stress to break through host barriers. High rates of interaction between humans and other animals provide a considerable trial and error experimental environment for viral pathogens to cross from one host to another, resulting in the emergence of new pathogens (Dolja & Koonin, 2018).
The evolutionary basis of CoV has made devastating comebacks possible; for example, the severe acute respiratory syndrome coronavirus (SARS-CoV) outbreak of 2002 - 2003 (Drosten et al., 2003; Holmes & Rambaut, 2004) that infected over 8,000 people with varying morbidity and mortality rates (Guarner, 2020). A new strain that emerged in the Middle East during 2012 (Middle East respiratory syndrome coronavirus; MERS-COV) that killed over 780 people were thought to arise due to Arabs interacting with dromedary camel products and by-products (Reusken et al., 2013). In 2013, a porcine epidemic diarrhea coronavirus (PEDV) with a 100% fatality rate that decimated 10% of the total pig population in the USA (Mole, 2013; Chen et al., 2014). The virus transformed and emerged within a decade of the PEDV epidemic in the form of COVID–19 with pneumonia-like symptoms. Such situations are becoming more problematic for authorities to manage. The epicenter of this virus is thought to be an animal market in Wuhan (Chang, Lu, Chen, Jin, & Yang, 2012)
SARS-CoV–2 has an ~29 kb genome, a GC content of 38%, and RNA that encodes various proteins including the structural spike (S), membrane (M), and envelope (E) proteins (Enjuanes, Almazán, Sola, & Zuñiga, 2006; Fehr & Perlman, 2015). The CoV S-protein is a glycoprotein that expresses pathogenic characteristics in hosts by interacting with various cellular receptors and invading cells (Kwak, Song, Lee, & Schiefelbein, 2015). S-proteins vary according to viral types and range from 1,160 to 1,400 amino acids that facilitate viral entry into cells by interaction with various receptors (Belouzard et al., 2012). S-proteins consist of an N-terminal domain, an S1 receptor-binding region, and a C-terminal S2 binding domain. The latter domain assists viral fusion with host receptors on cell membranes (Bosch, van der Zee, de Haan, & Rottier, 2003; Millet & Whittaker, 2015). The protein is cleaved during viral maturation and exocytosis in some viruses, which causes various distinctions among CoV isolates. S-protein is class 1 fusion protein with an α-helical structure that confers the features of similar coiled-coils such as influenza hemagglutinin protein HA (Bosch et al., 2003; Xu et al., 2004).
Receptor-mediated intracellular entry varies according to viral strains. Aminopeptidase N (APN) receptors are used by various α-CoV, HCoV-NL63 and SARS and they interact with angiotensin-converting enzyme 2 (ACE2) to mediate cellular entry, whereas the novel dipeptidyl-peptidase 4 (DPP4) confers invasive capability upon MERS-COV (Fehr & Perlman, 2015). Here, we analyzed the evolutionary changes in S-protein that allow the virus to penetrate host barriers and cause infection using specie based analysis. S-protein modifications and other mutations lead to protein evolution that helps viruses to invade new species. Viruses then undergo further modifications over several years that lead to the entry into and pathogenesis of more new hosts. In this study, we carried out an in silico based virtual screening based approach to find potential drug compound using natural compounds. Our findings will increase understanding of the mechanisms of CoV infection and possibly lead to therapeutic interventions against it. We also screened phytochemical inhibitors in a database of Ayurvediccompounds to identify agents that might act against S-protein.