Anisotine and amarogentin as promising inhibitory candidates against SARS-CoV-2 proteins: a computational investigation

Abstract

The coronavirus disease 2019 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents an unprecedented challenge to global public health with researchers striving to find a possible therapeutic candidate that could limit the spread of the virus. In this context, the present study employed an in silico molecular interaction-based approach to estimate the inhibitory potential of the phytochemicals from ethnomedicinally relevant Indian plants including Justicia adhatoda, Ocimum sanctum and Swertia chirata, with reported antiviral activities against crucial SARS-CoV-2 proteins. SARS-CoV-2 proteins associated with host attachment and viral replication namely, spike protein, main protease enzyme M^pro and RNA-dependent RNA polymerase (RdRp) are promising druggable targets for COVID-19 therapeutic research. Extensive molecular docking of the phytocompounds at the binding pockets of the viral proteins revealed their promising inhibitory potential. Subsequent assessment of physicochemical features and potential toxicity of the compounds followed by robust molecular dynamics simulations and analysis of MM-PBSA energy scoring function revealed anisotine against SARS-CoV-2 spike and M^pro proteins and amarogentin against SARS-CoV-2 RdRp as potential inhibitors. It was interesting to note that these compounds displayed significantly higher binding energy scores against the respective SARS-CoV-2 proteins compared to the relevant drugs that are currently being targeted against them. Present research findings confer scopes to explore further the potential of these compounds in vitro and in vivo towards deployment as efficient SARS-CoV-2 inhibitors and development of novel effective therapeutics.

Communicated by Ramaswamy H. Sarma

Keywords:

• SARS-CoV-2
• Justicia adhatoda
• Ocimum sanctum
• Swertia chirata
• phytocompounds
• molecular docking
• molecular dynamics simulations
• therapeutic candidates

Acknowledgments

PK would like to thank University of North Bengal, India for providing fellowship. VK acknowledges DST-SERB Startup Research Scheme (File No. SRG/2019/001279) and Lovely Professional University, India for the infrastructure support. BV would like to thank Bharathiar University, India and Project funded and supported by MHRD-RUSA 2.0 – BEICH 2.0 (Ref No.BU/RUSA/BEICH/2019/65) for providing the necessary infrastructure facility. AR acknowledges Lovely Professional University, India for the infrastructure support. The Mangosuthu University of Technology, South Africa is acknowledged by DN and AA for infrastructure facility. MDS would like to thank Indian Council of Medical Research (ICMR) (File No. 2018-2786/CMB/Adhoc-BMS) for providing the necessary infrastructure support.

Disclosure statement

The authors declare that they have no conflict of interest.