In silicoinvestigation of spice molecules as potent inhibitor of SARS-CoV-2

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel infectious disease that is in rapid growth. Several trials are going on worldwide to find a solution for this pandemic. The viral replication can be blocked by inhibiting the receptor-binding domain (RBD) of SARS-CoV-2 spike protein (SARS-CoV-2 RBD Spro) and the SARS-CoV-2 main protease (SARS-CoV-2 Mpro). The binding of potential small molecules to these proteins can inhibit the replication and transcription of the virus. The spice molecules that are used in our food have antiviral, antifungal and antimicrobial properties. As spice molecules are consumed in the diet, hence its antiviral properties against SARS-CoV-2 will benefit in a significant manner. Therefore, in this work, the molecular docking of 30 selected spice molecules (screened through ADME property) was performed to identify the potential inhibitors for the RBD Spro and Mpro of SARS-CoV-2. We have found that though all the molecules bind actively with the SARS-CoV-2 RBD Spro and Mpro, but Piperine has the highest binding affinity among the 30 screened molecules. Besides, the comparative study between Piperine and currently used drugs show that Piperine is more effective. The interaction of Piperine with RBD Spro and Mpro is further validated by the molecular dynamics (MD) simulation studies. The free energy landscape and binding free energy results also, support for the stable complex formation of Piperine with RBD Spro and Mpro. We anticipate immediate wet-lab experiments and clinical trials in support of this computational study that might help to inhibit the SARS-CoV-2 virus.

Dual inhibition of SARS-CoV-2 spike and main protease through a repurposed drug, rutin

“…angiotensinconverting enzyme 2 (ACE2), amino peptidase N (APN), dipeptidyl peptidase 4 (DPP4), carcinoembryonic antigenrelated cell adhesion molecule 1 (CEACAM1), and sugar recognize S1 domain of the spike protein to render virus entry into cells (Li, 2016). Several reports have been published recently discovering inhibitors against the target via a computational methodologies, which involve the usage of FDA approved compounds and natural compounds (Wei et al, 2020), spice molecules (Rout et al, 2020), small-molecule compounds of ZINC Drug Database (Kadioglu, 2020;Wu et al, 2020) along with traditional Chinese medicine and natural products and derivatives (Wu et al, 2020) and medicinal compounds (Salman et al, 2020).…”

“…Due to the availability of the crystal structure and the absence of any human homologue, the Mpro is a lucrative drug target to work upon for the discovery of novel antiviral agents (Jin et al, 2020;Wu et al, 2020;Zhang et al, 2020). Recently, numerous studies have emerged against this target, discovering novel inhibitors by utilizing computational approaches which include the use of natural molecules (Aanouz et al, 2020;Das et al, 2020), commercially available drugs and zinc library (Das et al, 2020;Elmezayen, 2020;Ton et al, 2020), antiviral compounds (Khan, 2020;Kumar et al, 2020;Muralidharan, 2020), peptide molecules (Pant, 2020), generative chemistry approaches for drug design (Alex, 2020), combinatorial strategy of using anti-virals, natural products, anti-fungals, anti-protozoals and anti-nematodes (Das et al, 2020), and spice molecules (Rout et al, 2020).…”

The Failures of Ethnobotany and Phytomedicine in Delivering Novel Treatments for Snakebite Envenomation

“…Even though these drugs have reached clinical phase III trial for cancer [35], the data so far in SBE show them to be comparable to many plant preparations as previously discussed. One example of such compounds is piperine, which has completed phase II for dysphagia [36], which is also supported by strong absorption and bioavailability data [37].…”

In silico evaluation of lapachol derivatives binding to the Nsp9 of SARS-CoV-2

“…This methodology has been used to design and identify potential ligands for viruses including Chikungunya virus, dengue virus, and SARS-CoV. For emergency development of antiviral agents, studies have focused on identifying drug targets among essential proteins in virus replication, primarily targeting conserved structures and enzymes such as RNA-dependent-RNA-polymerase (RdRp), main 3-chymotrypsin-like cysteine protease (M PRO ), or the receptor-binding domain (RBD) of SARS-CoV-2 spike protein (Bharadwaj et al., 2020 ; Buonaguro et al., 2020 ; Rout et al., 2020 ). However, many other targets are predicted to impact viral activity (Gordon et al., 2020 ; Wu et al., 2020 ).…”