SARS-CoV-2 mutation hotspots incidence in different geographic regions

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is RNA virus with a positive-sense single-strand that belongs to the beta-coronavirus group that causes COVID-19 (Coronavirus Disease 2019) which originally emerged in China. Viruses with RNA genomes are known by a high mutation rate potential. The mutation rate determines genome variability and evolution of the virus;therefore, allowing viruses to evade the immune system, gain more infectivity potentials, virulence modifications, and probably resistance development to antivirals. A total of 311 SARS-CoV-2 virus whole genome sequences have been retrieved from the GISAID database from 1st of January 2020 to 31th of August 2020. The sequences were analyzed for sequence purity and multiple sequence alignment together with reference sequence was conducted through using Clustal Omega that is imbedded in Jalview software and Blast tools. We recorded the occurrence of 4 newly incident high frequently occurring mutations in all six geographic regions, namely at positions 2416, 18877, 23401, and 27964. The majority of all recorded hotspots were detected in Asia, Europe, and North America. The findings of our study suggest that the SARS-CoV-2 is in continuous evolution. For the impact of these mutations, further investigations are required and to understand whether these mutations would lead to the appearance of Drug-resistance viral strains, strains with increased infectivity and pathogenicity, and also their effect on the vaccine development and immunogenesis.

In Silico Mining of Terpenes from Red-Sea Invertebrates for SARS-CoV-2 Main Protease (M^pro) Inhibitors

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for the COVID-19 pandemic, which generated more than 1.82 million deaths in 2020 alone, in addition to 83.8 million infections. Currently, there is no antiviral medication to treat COVID-19. In the search for drug leads, marine-derived metabolites are reported here as prospective SARS-CoV-2 inhibitors. Two hundred and twenty-seven terpene natural products isolated from the biodiverse Red-Sea ecosystem were screened for inhibitor activity against the SARS-CoV-2 main protease (M^pro) using molecular docking and molecular dynamics (MD) simulations combined with molecular mechanics/generalized Born surface area binding energy calculations. On the basis of in silico analyses, six terpenes demonstrated high potency as M^pro inhibitors with DELTAG_binding <= -40.0 kcal/mol. The stability and binding affinity of the most potent metabolite, erylosides B, were compared to the human immunodeficiency virus protease inhibitor, lopinavir. Erylosides B showed greater binding affinity towards SARS-CoV-2 M^pro than lopinavir over 100 ns with DELTAG_binding values of -51.9 vs. -33.6 kcal/mol, respectively. Protein-protein interactions indicate that erylosides B biochemical signaling shares gene components that mediate severe acute respiratory syndrome diseases, including the cytokine- and immune-signaling components BCL2L1, IL2, and PRKC. Pathway enrichment analysis and Boolean network modeling were performed towards a deep dissection and mining of the erylosides B target-function interactions. The current study identifies erylosides B as a promising anti-COVID-19 drug lead that warrants further in vitro and in vivo testing.