Frontiers in Immunology by Faez Iqbal Khan1, Fakhrul Hassan2 and Dakun Lai1 1/14/2022
In Silico Studies on Psilocybin Drug Derivatives Against SARS-CoV-2 and Cytokine Storm of Human Interleukin-6 Receptor
Various metabolites identified with therapeutic mushrooms have been found from different sources and are known to have antibacterial, antiviral, and anticancer properties. Over thousands soil growth-based mushroom metabolites have been discovered, and utilized worldwide to combat malignancy. In this study, psilocybin-mushroom that contains the psychedelic compounds such as psilacetin, psilocin, and psilocybine were screened and found to be inhibitors of SARS-CoV-2 Mprotease. It has been found that psilacetin, psilocin, and psilocybine bind to Mprotease with −6.0, −5.4, and −5.8 kcal/mol, respectively. Additionally, the psilacetin was found to inhibit human interleukin-6 receptors to reduce cytokine storm. The binding of psilacetin to Mprotease of SARS-CoV-2 and human interleukin-6 receptors changes the structural dynamics and Gibbs free energy patterns of proteins. These results suggested that psilocybin-mushroom could be utilized as viable potential chemotherapeutic agents for SARS-CoV-2.
Introduction
Coronaviruses (CoVs) represent the family Coronaviridae and sub-family Orthocoronavirinae. The sub family Orthocoronavirinae is further divided into four genera namely, α-coronavirus, β-coronavirus, γ-coronavirus, and δ coronavirus. The host of α- and β-coronaviruses are mammals, while the host of γ- and δ-coronaviruses are birds (1, 2). Some of the β-coronavirus like Severe Acute Respiratory Syndrome CoV 1 & 2 (SARS-CoV1 and SARS-CoV2), and Middle-East Respiratory Syndrome CoV (MERS-CoV) are the leading cause of pneumonia in this century. The outbreaks of SARS-CoV1, MERS-CoV and SARS-CoV2 were caused by zoonotic viruses in 2003, 2012 and 2019-20 with fatality ratio of 10%, 35% and 5%, respectively (3–8). The International Virus Classification Commission (ICTV), termed this 2019 novel CoV as SARS-CoV-2 (9, 10).
SARS-CoV-2 possesses the positive-sense single‐stranded ~30 kb RNA genome and consists of 12 open reading frames. The genes located on the 3′-terminus of the virus genome code for four structural proteins such as membrane glycoprotein (M), envelope (E), nucleocapsid (N), spike (S) and eight accessory such as 3a, 3b, p6, 7a, 7b, 8b, 9b, and ORF14 proteins (11, 12). ORFIa and ORF1ab genes encode the non-structural proteins that form the replication/transcription complex, respectively. These genes such as ORFIa and ORF1ab encode two polypeptides called pp1a and pp1ab, respectively. The polypeptides are directly translated and catalytically processed by main protease (Mprotease).
Mprotease is accountable for the cleavage of polyprotein downstream of non-structural protein 4 to form distinctive non-structural proteins that show important roles in the life cycle of the virus (13, 14).
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https://www.frontiersin.org/articles/10.3389/fimmu.2021.794780/full
