Suramin, penciclovir, and anidulafungin exhibit potential in the treatment of COVID-19 via binding to nsp12 of SARS-CoV-2

Abstract

COVID-19, for which no confirmed therapeutic agents are available, has claimed over 48,14,000 lives globally. A feasible and quicker method to resolve this problem may be ‘drug repositioning’. We investigated selected FDA and WHO-EML approved drugs based on their previously promising potential as antivirals, antibacterials or antifungals. These drugs were docked onto the nsp12 protein, which reigns the RNA-dependent RNA polymerase activity of SARS-CoV-2, a key therapeutic target for coronaviruses. Docked complexes were reevaluated using MM-GBSA analysis and the top three inhibitor-protein complexes were subjected to 100 ns long molecular dynamics simulation followed by another round of MM-GBSA analysis. The RMSF plots, binding energies and the mode of physicochemical interaction of the active site of the protein with the drugs were evaluated. Suramin, Penciclovir, and Anidulafungin were found to bind to nsp12 with similar binding energies as that of Remdesivir, which has been used as a therapy for COVID-19. In addition, recent experimental evidences indicate that these drugs exhibit antiviral efficacy against SARS-CoV-2. Such evidence, along with the significant and varied physical interactions of these drugs with the key viral enzyme outlined in this investigation, indicates that they might have a prospective therapeutic potential in the treatment of COVID-19 as monotherapy or combination therapy with Remdesivir.

Graphical Abstract

Communicated by Ramaswamy H. Sarma

Keywords:

• SARS-CoV-2
• RdRp
• Non-Structural Protein 12
• FDA approved Drugs
• WHO-EML
• COVID-19
• Suramin
• Penciclovir and Anidulafungin

Acknowledgements

SKD is thankful to Professor Eddy Arnold, Rutgers University, USA, for the opportunity to carry out some of the investigation in his laboratory; the University of Delhi and its Dr. B.R. Ambedkar Center for Biomedical Research (ACBR) to conduct the updated experiments and providing infrastructures as well as financial support for the same. MS and SB acknowledge the Department of Biotechnology (DBT), Government of India for their project and research fellowships, respectively. CD appreciates the financial support from Lady Tata Memorial Trust in the form of a research fellowship. ASR is thankful to the Government of Odisha for the Biju Patnaik Research Fellowship. SK appreciates financial support over the years from DBT, University Grants Commission (UGC), Defence Research and Development Organization (DRDO) and Department of Science and Technology (DST), Government of India. SK is thankful to the University of Delhi, Institution of Eminence, for support in all forms.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

SK Dey acknowledges financial support from Prof. Eddy Arnold, Rutgers University, USA; University of Delhi (R & D Grants); and Dr. B.R. Ambedkar Center for Biomedical Research [ACBR] (R & D Grants), University of Delhi; M Saini acknowledges the Senior Research Fellowship from a DBT funded project [Project No.: BT/PR13531/MED/30/1523/2015] and non-NET fellowship from the University of Delhi; S Bhatt acknowledges the Department of Biotechnology (DBT), Government of India for a research fellowship. C Dhembla appreciates the financial support from Lady Tata Memorial Trust in the form of a research fellowship. A S Rajesh is thankful to the Government of Odisha for the Biju Patnaik Research Fellowship. S Kundu acknowledges the financial support from DBT, Government of India through extramural projects [BT/PR8391/BRB/10/1231/2013; BT/COE/34/SP15246/2015 and BT/PR13531/MED/30/1523/2015]. S Kundu also acknowledges financial support from the University of Delhi (R & D Grant; Institution of Eminence grant IOE/FRP/LS/2020/27); UGC, Government of India (SAP program) and DST, Government of India (PURSE Program).