Abstract
Due to the rapid growth of the COVID-19 pandemic and its outcomes, developing a remedy to fight the predicament is critical. So far, it has infected more than 214,468,601 million people and caused the death of 4,470,969 million people according to the August 27, 2021, World Health Organization's (WHO) report. Several studies have been published on both computational and wet-lab approaches to develop antivirals for COVID-19, although there has been no success yet. However, the wet-lab approach is laborious, expensive, and time-consuming, and computational techniques have screened the activity of bioactive compounds from different sources with less effort and cost. For this investigation, we screened the binding affinity of fungi-derived bioactive molecules toward the SARS coronavirus papain-like protease (PLpro) by using computational approaches. Studies showed that protease inhibitors can be very effective in controlling virus-induced infections. Additionally, fungi represent a vast source of bioactive molecules, which could be potentially used for antiviral therapy. Fifty fungi-derived bioactive compounds were investigated concerning SARS-CoV-2 PLpro by using Auto Dock 4.2.1, Gromacs 2018. 2, ADMET, Swiss-ADME, FAF-Drugs 4.023, pKCSM, and UCLA-DOE server. From the list of the screened bioactive compounds, Dihydroaltersolanol C, Anthraquinone, Nigbeauvin A, and Catechin were selected with the Auto-Dock results of −8.68, −7.52, −10.46, and −10.58 Kcal/mol, respectively, based on their binding affinity compared to the reference drug. We presented the drug likeliness, toxicity, carcinogenicity, and mutagenicity of all compounds using ADMET analysis. They interacted with the amino acid residues, Gly163, Trp106, Ser111, Asp164, and Cys270, through hydrogen bonds. The root-mean-square deviation (RMSD), root-mean-square fluctuations (RMSF), solvent-accessible surface area (SASA), and radius of gyration (Rg) values revealed a stable interaction. From the overall analyses, we can conclude that Dihydroaltersolanol C, Anthraquinone, Nigbeauvin A, and Catechin are classified as promising candidates for PLpro, thus potentially useful in developing a medicine for COVID-19.
Highlights
The SARS-CoV-2 virus causes a lethal infection of the respiratory system
With the urgent need for safe and effective drugs to treat COVID-19, we have explored bioactive molecules isolated from fungi that have been reported to possess an anti-HIV protease [13,14,15,16, 18,19,20]
The Papain-like protease (PLpro)-Nigbeauvin A complex and PLpro-Anthraquinone were stabilized by one hydrogen bond each at Asp164 and Gly163 positions, respectively, whereas Dihydroaltersolanol interacted with PLpro through three conventional hydrogen bonds at Glu167, Lys157, and Asp164 positions (Figure 1 and Table 1), which are consistent with the previous findings conducted by targeting the PLpro [7]
Summary
The SARS-CoV-2 virus causes a lethal infection of the respiratory system. Most people infected with the virus showed mild to severe respiratory illness, while others were able to recover without demanding treatment [1]. Papain-like protease (PLpro) is an essential coronavirus protein required for the processing of viral polyproteins to generate functional protein for virus replication and enable viral spread; the inhibition of the PLpro is a feasible strategy to develop antiviral drugs and suppress the ongoing SARS-CoV2 impacts [3,4,5]. They are unique to the different viruses including COVID-19, offering the potential for specific treatments that produce minimal toxic side effects [5]. We screened the interaction of a library of fungi-derived bioactive molecules against PLpro as inhibitors with binding pocket residues
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