Predictive Insights Into Bioactive Compounds from Streptomyces as Inhibitors of SARS-CoV-2 Mutant Strains by Receptor...

Area of Science:

• Virology and Drug Discovery
• Computational Chemistry and Molecular Modeling

Background:

• The SARS-CoV-2 spike protein's receptor-binding domain (RBD) interacts with human ACE2.
• Numerous SARS-CoV-2 variants with mutations in the RBD have emerged, impacting transmissibility, pathogenicity, diagnostics, and vaccine effectiveness.
• Existing SARS-CoV-2 therapeutics offer limited efficacy against resistant variants.

Purpose of the Study:

• To discover a novel compound with potent antiviral activity against SARS-CoV-2 variants.
• To identify natural products capable of inhibiting the interaction between SARS-CoV-2 RBD and ACE2.

Main Methods:

• Structure-based virtual screening of natural products from the StreptomeDB database.
• Targeting the ACE2-binding pocket of the SARS-CoV-2 RBD, including wild-type and variant strains (Alpha, Beta, Delta, Lambda, Omicron/BA.1, Omicron/BA.2).
• Molecular dynamics simulations of identified complexes over 100 ns.

Main Results:

• Stambomycin B was identified as a lead compound with the highest binding affinity to the SARS-CoV-2 RBD.
• Molecular dynamics simulations confirmed Stambomycin B's potential to effectively inhibit various SARS-CoV-2 variants.
• The compound demonstrated favorable binding interactions within the ACE2-binding pocket.

Conclusions:

• Stambomycin B, a macrolide produced by *Streptomyces ambofaciens*, is a promising natural product candidate.
• It may effectively combat current and future SARS-CoV-2 variants by inhibiting RBD-ACE2 binding.
• Further research into Stambomycin B as an antiviral therapeutic is warranted.