Abstract
The COVID-19 pandemic caused unprecedented damage to humanity, and while vaccines have been developed, they are not fully effective against the SARS-CoV-2 virus. Limited targeted drugs, such as Remdesivir and Paxlovid, are available against the virus. Hence, there is an urgent need to explore and develop new drugs to combat COVID-19. This study focuses on exploring microbial natural products from soil-isolated bacteria Streptomyces sp. strain 196 and RI.24 as a potential source of new targeted drugs against SARS-CoV-2. Molecular docking studies were performed on holoRdRp and nsp13, two key factors responsible for virus replication factor. Our in silico studies, K-252-C aglycone indolocarbazole alkaloid (K252C) and daunorubicin were found to have better binding affinities than the respective control drugs, with K252C exhibiting binding energy of − 9.1 kcal/mol with holoRdRp and − 9.2 kcal/mol with nsp13, and daunorubicin showing binding energy at − 8.1 kcal/mol with holoRdRp and − 9.3 kcal/mol with nsp13. ADMET analysis, MD simulation, and MM/GBSA studies indicated that K252C and daunorubicin have the potential to be developed as targeted drugs against SARS-CoV-2. The study concludes that K252C and daunorubicin are potential lead compounds that might suppress the inhibition of SARS-CoV-2 replication among the tested microbial compounds and could be developed as targeted drugs against COVID-19. In the future, further in vitro studies are required to validate these findings.
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Authors are thankful to Department of Zoology, University of Allahabad and Microbial Technology Lab, Acharya Narendra Dev College, University of Delhi.
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Formal analysis: PK, P, NR, MK and SK; investigation: PK, P and NR; methodology: PK, P, KUF and SK; supervision: PK, NM and MKK; visualization: PK and AMA; writing: original draft: PK, P, NR, MK, SK, KUF, AAK, RS and H.
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Kumar, P., Parveen, Raj, N. et al. Natural products from Streptomyces spp. as potential inhibitors of the major factors (holoRdRp and nsp13) for SARS-CoV-2 replication: an in silico approach. Arch Microbiol 206, 88 (2024). https://doi.org/10.1007/s00203-023-03820-5
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DOI: https://doi.org/10.1007/s00203-023-03820-5