Mohammad Hassan Baig, Ayman Turk, Preeti Vishwakarma, Yun Seong Jo, Jae-June Dong, Dae Hee Lee, Young Guk Kim, Mi Kyeong Lee, Jae-Yong Cho
{"title":"Exploring the Therapeutic Potential of <i>Cordyceps</i> Mushroom on SARS-CoV-2 Using Virtual Screening against M<sup>pro</sup> and In Vitro Validation of Cordycepin.","authors":"Mohammad Hassan Baig, Ayman Turk, Preeti Vishwakarma, Yun Seong Jo, Jae-June Dong, Dae Hee Lee, Young Guk Kim, Mi Kyeong Lee, Jae-Yong Cho","doi":"10.4014/jmb.2411.11063","DOIUrl":null,"url":null,"abstract":"<p><p>Pathogenic coronavirus, including COVID-19, threatens human health, and there have been strong demands for efficient therapeutics. <i>Cordyceps militaris</i> is a medicinal mushroom that has long been used for immune enhancement, anticancer, and antiviral effects. Therefore, the inhibitory potentials of constituents of <i>C. militaris</i> against COVID-19 were analyzed using various virtual screening analyses. Among ten constituents of <i>C. militaris</i>, cordycepin, the major component, and 3'-deoxyuridine and 2'-<i>O</i>-methyl-adenosine showed strong binding affinity to M<sup>pro</sup>, a potential target for COVID-19 therapeutics. Considering the structure-activity relationship, nucleosides having deoxyribose and methoxyribose moiety are important for the affinity to M<sup>pro</sup>. Cordycepin is also bound to M<sup>pro</sup> mutants, and the binding mechanisms between cordycepin and M<sup>pro</sup> were investigated further by MD simulation and MM/PBSA analysis. Principal component analysis also confirmed the conformational change of M<sup>pro</sup> by cordycepin, which inhibits the function of M<sup>pro</sup>. <i>In vitro</i>, the efficacy of cordycepin was measured using Vero cells infected with SARS-CoV-2, which showed excellent inhibition with an IC<sub>50</sub> value of 29 μM. Conclusively, the constituents of <i>C. militaris</i> are expected to inhibit SARS-CoV-2 replication through binding to M<sup>pro</sup>. Therefore, <i>C. militaris</i> can be an essential therapeutic for coronavirus through the synergistic effect of its constituents.</p>","PeriodicalId":16481,"journal":{"name":"Journal of microbiology and biotechnology","volume":"35 ","pages":"e2411063"},"PeriodicalIF":2.5000,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of microbiology and biotechnology","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.4014/jmb.2411.11063","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Pathogenic coronavirus, including COVID-19, threatens human health, and there have been strong demands for efficient therapeutics. Cordyceps militaris is a medicinal mushroom that has long been used for immune enhancement, anticancer, and antiviral effects. Therefore, the inhibitory potentials of constituents of C. militaris against COVID-19 were analyzed using various virtual screening analyses. Among ten constituents of C. militaris, cordycepin, the major component, and 3'-deoxyuridine and 2'-O-methyl-adenosine showed strong binding affinity to Mpro, a potential target for COVID-19 therapeutics. Considering the structure-activity relationship, nucleosides having deoxyribose and methoxyribose moiety are important for the affinity to Mpro. Cordycepin is also bound to Mpro mutants, and the binding mechanisms between cordycepin and Mpro were investigated further by MD simulation and MM/PBSA analysis. Principal component analysis also confirmed the conformational change of Mpro by cordycepin, which inhibits the function of Mpro. In vitro, the efficacy of cordycepin was measured using Vero cells infected with SARS-CoV-2, which showed excellent inhibition with an IC50 value of 29 μM. Conclusively, the constituents of C. militaris are expected to inhibit SARS-CoV-2 replication through binding to Mpro. Therefore, C. militaris can be an essential therapeutic for coronavirus through the synergistic effect of its constituents.
期刊介绍:
The Journal of Microbiology and Biotechnology (JMB) is a monthly international journal devoted to the advancement and dissemination of scientific knowledge pertaining to microbiology, biotechnology, and related academic disciplines. It covers various scientific and technological aspects of Molecular and Cellular Microbiology, Environmental Microbiology and Biotechnology, Food Biotechnology, and Biotechnology and Bioengineering (subcategories are listed below). Launched in March 1991, the JMB is published by the Korean Society for Microbiology and Biotechnology (KMB) and distributed worldwide.