In Silico Study of Alkaloids: Neferine and Berbamine Potentially Inhibit the SARS-CoV-2 RNA-Dependent RNA Polymerase

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, has been a global concern. While there have been some vaccines and drugs, the rapid emergence of variants due to mutations has threatened public health. As the de novo drug development process is expensive and time-consuming, repurposing existing antiviral drugs against SARS-CoV-2 is an alternative and promising approach to mitigate the current situation. Several studies have indicated that some natural products exhibit inhibitory activities against SARS-CoV-2. This study is aimed at analyzing the potential of natural alkaloids, using various computational tools, as drug candidates against SARS-CoV-2. The molecular docking analysis predicted that naturally occurring alkaloids can bind with RNA-dependent RNA-polymerase (RdRP). The QSAR analysis was conducted by using the way2drug/PASS online web resource, and the pharmacokinetics and toxicity properties of these alkaloids were predicted using pkCSM, SwissADME, and ProTox-II webserver. Among the different alkaloids studied, neferine and berbamine were repurposed as potential drug candidates based on their binding affinity and interactions with RdRP. Further, molecular dynamics simulation of 90 ns revealed the conformational stability of the neferine-RdRP complex.

Molecular Docking and Dynamics Simulation of Several Flavonoids Predict Cyanidin as an Effective Drug Candidate against SARS-CoV-2 Spike Protein

“…Despite continued efforts from various research groups, no effective drug against COVID-19 has been developed yet. In the search for a safe and effective drug, the computational approach provides a good platform for the virtual screening of metabolites to select potential drug candidates [ 57 ]. Therefore, repurposing natural secondary metabolites could be the most effective way to discover a remedy for COVID-19 infection [ 58 ].…”

Discovery of Natural Bisbenzylisoquinoline Analogs from the Library of Thai Traditional Plants as SARS-CoV-2 3CLPro Inhibitors: In Silico Molecular Docking, Molecular Dynamics, and In Vitro Enzymatic Activity

“…Emetine demonstrated the effective antiviral activity on SARS-CoV-2 infected Vero E6 cells with the IC 50 value around 0.5 μM and also exhibited the synergistic effect in drug combination with the available antiviral drug remdesivir . Furthermore, other isoquinoline alkaloids with antiviral activity on SARS-CoV-2 were fangchinoline, cepharanthine, hernandezine, and tetrandrine. , Moreover, plenty of in silico studies also encouraged that these compound classes had the potential for further development as antiviral agents for COVID-19 treatment. − …”

Effects of Bacterial Metabolites on the Wnt4 Protein in Dental-Pulp-Stem-Cells-Based Endodontic Pulpitis Treatment

“…SASA (solvent-accessible surface area) plots are used to measure the solvent exposure of a protein’s structure. Lower SASA values correspond to increased hydrophobic amino acid residues, which can contribute to increased system stability [ 30 ]. We observed marginal differences in the SASA plot of free Wnt4 and the Wnt4 complex, with SASA averages of 190.96 nm 2 and 192.11 nm 2 , respectively ( Figure 5 ).…”