Identifying inhibitors of NSP16-NSP10 of SARS-CoV-2 from large databases

Abstract

The COVID-19 pandemic, which has already claimed millions of lives, continues to pose a serious threat to human health, requiring the development of new effective drugs. Non-structural proteins of SARS-CoV-2 play an important role in viral replication and infection. Among them, NSP16 (non-structured protein 16) and its cofactor NSP10 (non-structured protein 10) perform C2'-O methylation at the 5' end of the viral RNA, which promotes efficient virus replication. Therefore, the NSP16-NSP10 complex becomes an attractive target for drug development. Using a multi-step virtual screening protocol which includes Lipinski’s rule, docking, steered molecular dynamics and umbrella sampling, we searched for potential inhibitors from the PubChem and anti-HIV databases. It has been shown that CID 135566620 compound from PubChem is the best candidate with an inhibition constant in the sub-μM range. The Van der Waals interaction was found to be more important than the electrostatic interaction in the binding affinity of this compound to NSP16-NSP10. Further in vitro and in vivo studies are needed to test the activity of the identified compound against COVID-19.

Communicated by Ramaswamy H. Sarma

Keywords:

• Virtual screening
• SARS-CoV
• COVID-19
• SARS-CoV-2 (nCoV)
• umbrella sampling
• NSP16-NSP10
• COVID-19

Disclosure statement

The authors declare no competing financial interest.

Additional information

Funding

This work was supported by Narodowe Centrum Nauki in Poland (Grant 2019/35/B/ST4/02086), the Department of Science and Technology at Ho Chi Minh city (Grant 45/2020/HD-QPTKHCN), the TASK Supercomputer Center in Gdansk, PLGrid Infrastructure, Poland and the HPCC at the Institute for Computational Science and Technology, Ho Chi Minh City, Vietnam. Hoang Linh Nguyen was funded by Vingroup JSC and supported by the Master, PhD Scholarship Programme of Vingroup Innovation Foundation (VINIF), Institute of Big Data, code VINIF.2021.TS.029.