Can Structural Differences Between SARS-CoV and SARS-CoV-2 Explain Differences in Drug Efficacy?
Keywords:SARS-CoV-2, ACE-2 receptors, RBD, Docking, Score
The severe acute respiratory syndrome corona virus (SARS-CoV)and severe acute respiratory syndrome corona virus-2 (SARS-CoV-2), both virus spike proteins are recognized by the cell surface receptors, human angiotensin converting enzyme-2 (ACE-2).These viruses gain access into the host cell through ACE-2receptors.The main aim of the current study was to elaborate on the structural differences in the receptor binding domain (RBD) of spike glycoprotein in SARS-CoV and SARS-CoV-2 that bind at the same active binding site. The crystal structures of receptor bound spikes of SARS-CoV and SARS-CoV-2 were compared using UCSF Chimera and pyMOL software which revealed significant differences in the receptor binding domain of the spikes with variation in the amino acid residues. It was also observed that conformational changes occurred in the amino acid residues at the binding site on ACE-2 receptor. These conformational changes in ACE-2 binding site of SARS-CoV-2 were attributed to a greater number of contacts forming between RBD and active binding site when compared to that of SARS-CoV and could explain any differences in the effectiveness of drugs against SARS-CoV and SARS-CoV-2. In addition, using Autodock vina software, drugs that were found to be effective in SARS-COV treatment were docked at active binding site on ACE-2.Antivirals, ACE-2 inhibitors and corticosteroids were docked at the active binding site domains of ACE-2 receptor in SARS-CoV andSARS-CoV-2.Antivirals such as Oseltamivir, Umifenovir, Favipiravir, Remdesivir and antibiotics such as Moxifloxacin and Azithromycin, Ace-2. Antivirals inhibitors such as Losartan and steroids such as Dexamethasone have shown a greater negative docking score (indicating more binding affinity) in and SARS-CoV-2 when compared to that of SARS-CoV. This kind of preliminary analysis using computational techniques could help in screening and repurposing the existing drugs that are potential in treating new diseases such as CoVID-19.