In-silico Investigation and Potential Therapeutic Approaches of Acanthus montanus for COVID-19: Computer-aided Drug Design Perspective

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a significant number of fatalities globally, establishing it as a critical and urgent public health concern.  Phytochemicals may serve as a valuable source of effective and safer therapeutic agents against SARS-CoV-2.  The lack of sanctioned treatments or vaccinations remains a significant concern, necessitating the development of novel pharmaceuticals.  Computer-aided drug design has significantly accelerated the drug research and development process by reducing both costs and time. Natural compounds derivatives demonstrate significant effects on viral replication and support future research in the development of novel therapeutics. Acanthus montanus (Nees) T. Anderson (Acanthaceae) is notable shrubby herb, which is commonly used for culinary and medicinal purposes. This study seeks to assess and evaluate the bioactive compounds present in Acanthaceae leaves that may be utilized in drug design for the treatment of COVID-19. The crystal structure of the SARS-CoV-2 main protease was obtained from a protein sequence database, specifically the Protein Data Bank. The bioactive compounds in Acanthaceae were identified through Gas Chromatography-Mass Spectrometry (GC-MS) analysis and High-Performance Liquid Chromatography (HPLC) analysis. The main protease of SARS-CoV-2 plays a critical role in the synthesis of polyproteins, which encompasses viral maturation and the assembly of nonstructural proteins, thereby positioning it as a promising target for antiviral intervention. Additionally, the bioactive compounds within the Acanthaceae family were evaluated in accordance with Lipinski’s rule of five to assess their drug-like molecular characteristics. Furthermore, molecular docking analysis was performed utilizing the PyRx (version 0.8) software, and a comprehensive examination of the interactions between SARS-CoV-2 and the bioactive compounds in Acanthaceae was carried out using the computational software. Among the 19 bioactive compounds that were successfully docked, Naringin, Kaempferol, Progesterol, Quercetin, Stigmasterol, and Rutin trihydrate exhibited the lowest binding energy against SARS-CoV-2, according to the virtual screening results. These compounds demonstrate significant potential as viral inhibitors of SARS-CoV-2 when compared to the standard drug Nirmatrelvir. Additional in vivo and in vitro investigations are recommended to validate the findings of this study and to furnish more robust evidence.