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During the Covid-19 pandemic, the resurgence of SARS-CoV-2 was due to the development of novel variants of concern (VOC). Thus, genomic surveillance is essential to monitor continuing evolution of SARS-CoV-2 and to track the emergence of novel variants. In this study, we performed phylogenetic, mutation, and selection pressure analyses of the Spike, nsp12, nsp3, and nsp5 genes of SARS-CoV-2 isolates circulating in Yogyakarta and Central Java provinces, Indonesia from May 2021 to February 2022. Various bioinformatics tools were employed to investigate the evolutionary dynamics of distinct SARS-CoV-2 isolates. During the study period, 213 and 139 isolates of Omicron and Delta variants were identified, respectively. Particularly in the Spike gene, mutations were significantly more abundant in Omicron than in Delta variants. Consistently, in all of four genes studied, the substitution rates of Omicron were higher than that of Delta variants, especially in the Spike and nsp12 genes. In addition, selective pressure analysis revealed several sites that were positively selected in particular genes, implying that these sites were functionally essential for virus evolution. In conclusion, our study demonstrated a distinct evolutionary pattern of SARS-CoV-2 variants circulating in Yogyakarta and Central Java provinces, Indonesia. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 belongs to Coronaviridae family infects host cells by the interaction of its spike glycoprotein and angiotensin-converting enzyme 2 (ACE 2) of host cells. Upon entry, the virus uses its RNA dependent RNA polymerase (NSP12) for transcribing its genome to survive in the cell and spread its infection. The protein sequences of receptor-binding domain (RBD) of spike glycoprotein, and NSP12 exhibits high homology in the family of Coronoviridae and are ideal candidates for the development of anti-coronaviral drugs. In the quest to identify inhibitory molecules against these proteins, we searched several molecules that are present in naturally occurring medicinal plants database. Andrographolide which is largely present in the leaf extracts of Andrographis paniculata (AP) and is known to exhibit antiviral, antibacterial, and stabilizes Th1/Th2/Th17 responses; taking this clue, we used in silico approaches to see the binding of andrographolide to RBD and NSP12 molecules. Our docking results showed very strong affinity of andrographolide to RBD and NSP12 of the SARS-CoV-2 virus with dock scores of −10.3460 for RBD and −10.7313 for NSP12 indicating andrographolide acts as an inhibitor of RBD and NSP12. These unique properties of andrographolide, AP extract, can be tested as anti-coronaviral drug. [ABSTRACT FROM AUTHOR]

COVID-19 has emerged as a rapidly escalating serious global health issue, affecting every section of population in a detrimental way. Present situation invigorated researchers to look for potent targets, development as well as repurposing of conventional therapeutic drugs. NSP12, a RNA polymerase, is key player in viral RNA replication and, hence, viral multiplication. In our study, we have screened a battery of FDA-approved drugs against SARS-CoV-2 RNA polymerase using in silico molecular docking approach. Identification of potent inhibitors against SARS-CoV-2 NSP12 (RNA polymerase) were screeened from FDA approved drugs by virtual screening for therapeutic applications in treatment of COVID-19. In this study, virtual screening of 1749 antiviral drugs was executed using AutoDock Vina in PyRx software. Binding affinities between NSP12 and drug molecules were determined using Ligplot+ and PyMOL was used for visualization of docking between interacting residues. Screening of 1749 compounds resulted in 14 compounds that rendered high binding affinity for NSP12 target molecule. Out of 14 compounds, 5 compounds which include 3a (Paritaprevir), 3d (Glecaprevir), 3h (Velpatasvir), 3j (Remdesivir) and 3l (Ribavirin) had a binding affinity of − 10.2 kcal/mol, −9.6 kcal/mol, − 8.5 kcal/mol, − 8.0 kcal/mol and − 6.8 kcal/mol, respectively. Moreover, a number of hydrophobic interactions and hydrogen bonding between these 5 compounds and NSP12 active site were observed. Further, 3l (Ribavirin) was docked with 6M71 and molecular dynamic simulation of the complex was also performed to check the stability of the conformation. In silico analysis postulated the potential of conventional antiviral drugs in treatment of COVID-19. However, these finding may be further supported by experimental data for its possible clinical application in present scenario. [ABSTRACT FROM AUTHOR]