Pharmacophore modelling of vanillin derivatives, favipiravir, chloroquine, hydroxychloroquine, monolaurin and tetrodotox
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RESEARCH NOTE
Pharmacophore modelling of vanillin derivatives, favipiravir, chloroquine, hydroxychloroquine, monolaurin and tetrodotoxin as MPro inhibitors of severe acute respiratory syndrome coronavirus‑2 (SARS‑CoV‑2) Woon Yi Law*, Mohd Razip Asaruddin*, Showkat Ahamd Bhawani and Samsur Mohamad
Abstract Objectives: The aim of this study was to use Ligand-based pharmacophore modelling approach for four established antiviral drugs, namely remdesivir, lopinavir, ritonavir and hydroxychloroquine for COVID-19 inhibitors as training sets. In this study Twenty vanillin derivatives together with monolaurin and tetrodotoxin were used as test sets to evaluate as potential SARS-CoV-2 inhibitors. The Structure-based pharmacophore modelling approach was also performed using 5RE6, 5REX and 5RFZ in order to analyse the binding site and ligand–protein complex interactions. Results: The pharmacophore modelling mode of 5RE6 displayed two Hydrogen Bond Acceptors (HBA) and one Hydrophobic (HY) interaction. Besides, the pharmacophore model of 5REX showed two HBA and two HY interactions. Finally, the pharmacophore model of 5RFZ showed three HBA and one HY interaction. Based on ligand-based approach, 20 Schiff-based vanillin derivatives, showed strong MPro inhibition activity. This was due to their good alignment and common features to PDB-5RE6. Similarly, monolaurin and tetrodotoxin displayed some significant activity against SARS-CoV-2. From structure-based approach, vanillin derivatives (1) to (12) displayed some potent M Pro inhibition against SARS-CoV-2. Favipiravir, chloroquine and hydroxychloroquine also showed some significant M Pro inhibition. Keywords: Coronavirus, Pharmacophore modelling, Vanillin, Favipiravir, Chloroquine, Hydroxychloroquine, Monolaurin, Tetrodotoxin Introduction In the early twenty-first century, an outbreak of coronaviruses has been causing a number of diseases. Coronavirus belong to the family of Coronaviridae. Coronaviruses are enveloped, positive-sense, single stranded RNA viruses, *Correspondence: [email protected]; [email protected] Faculty of Resource Science and Technology, Universiti Malaysia Sarawak, 94300 Kota Samarahan, Sarawak, Malaysia
with their size approximately 27 to 34 kilobases [1, 2]. Out of numerous coronaviruses, seven types of coronaviruses are known for their ability to cause infections and respiratory illnesses in humans [3]. Four types of coronaviruses: 229E, OC43, NL63, and HKU1 are associated with the symptoms of common cold [4]. Another two types of coronaviruses, which are severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) were the
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