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外文期刊>Journal of King Saud University
>Enhanced production of camptothecin by immobilized callus of Ophiorrhiza mungos and a bioinformatic insight into its potential antiviral effect against SARS-CoV-2
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Enhanced production of camptothecin by immobilized callus of Ophiorrhiza mungos and a bioinformatic insight into its potential antiviral effect against SARS-CoV-2
Camptothetin (CPT) is a quinoline alkaloid originally isolated from the Chinese tree,Camptotheca acuminata Decne. CPT was found to have anticancerous and antiviral properties. Derivatives of natural CPT, including topothecan and irinotecan are used clinically to treat a variety of cancers. Apart fromCamptotheca acuminata Decne,CPT production was also found in the perennial plantOphiorrhiza mungos.In this study we attempted the immobilization of the tissue culture grown callus ofOphiorrhiza mungosfor the continuous production of a higher concentration of CPT. As evident from previous studies about the antiviral effects of CPT, we wanted to bioinformatically analyze the binding potential of CPT towards two important proteins of SARS-CoV-2, protease (Mpro) and RNA dependent RNA polymerase (RdRp). Further docking analysis of the CPT against the exterior spike glycoprotein of SARS-CoV-2 was also done to determine their potential interaction. The immobilized callus ofOphiorrhiza mungosproduced CPT at a concentration of 420?μg/l by the end of 12?days of growth. The HPLC analysis was done to determine the purity of the CPT synthesized by the immobilization technique. The bioinformatic analysis revealed a higher binding efficiency of CPT and its derivatives, toptecan and irinotecan against Mproand RdRp. The docking analysis of CPT against the spike glycoprotein of SARS-CoV-2 showed hydrogen bonding with the amino acids at K466 with a bond distance of 2.56A° and K355 with a bond distance of 2.40A°. This finding was of particular importance that other compounds including hydroxychloroquine sulphate, lopinavir and ivermectin could bind with the spike protein only by weak Vander wall bonds and no hydrogen bond formation was noticed. Our studies hence evaluate the efficiency of CPT against SARS-CoV-2, by potentially blocking the interaction of the spike glycoprotein with the angiotensin-converting enzyme 2 (ACE2) receptor found on host cells.
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