Molecular docking of secondary metabolites from Indonesian marine and terrestrial organisms targeting SARS-CoV-2 ACE-2, M pro, and PL pro receptors

Abstract

With the uncontrolled spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), development and distribution of antiviral drugs and vaccines have gained tremendous importance. This study focused on two viral proteases namely main protease (Mpro) and papain-like protease (PLpro) and human angiotensin-converting enzyme (ACE-2) to identify which of these are essential for viral replication. We screened 102 secondary metabolites against SARS-CoV-2 isolated from 36 terrestrial plants and 36 marine organisms from Indonesian biodiversity. These organisms are typically presumed to have antiviral effects, and some of them have been used as an immunomodulatory activity in traditional medicine. For the molecular docking procedure to obtain Gibbs free energy value (∆G), toxicity, ADME and Lipinski, AutoDock Vina was used. In this study, five secondary metabolites, namely corilagin, dieckol, phlorofucofuroeckol A, proanthocyanidins, and isovitexin, were found to inhibit ACE-2, Mpro, and PLpro receptors in SARS-CoV-2, with a high affinity to the same sites of ptilidepsin, remdesivir, and chloroquine as the control molecules. This study was delimited to molecular docking without any validation by simulations concerned with molecular dynamics. The interactions with two viral proteases and human ACE-2 may play a key role in developing antiviral drugs for five active compounds. In future, we intend to investigate antiviral drugs and the mechanisms of action by in vitro study.

Potency of moringa (Moringa oleifera L.) leaves extract containing quercetin as a depigmentation agent inhibiting the tyrosinase enzyme using in-silico and in-vitro assay

“…A low energy value indicated an interaction in the form of a greater attraction between atoms. In contrast, the repulsion between atoms became less so that the conformation of the compound obtained was more stable than before the optimization process was conducted (Syahputra et al 2021) Docking between quercetin and tyrosinase target protein produces a bond energy value of -7.08 kcal/mol (Table 1). At the same time, the tropolone (native ligand) interact with the target protein tyrosinase enzyme produces a bond energy value of -4.79 kcal/mol (Table 1).…”

Seaweeds and Their Natural Products for Preventing Cardiovascular Associated Dysfunction

“…Syahputra et al screened secondary metabolites against SARS-CoV-2 isolated from 36 marine organisms with high biodiversity from Indonesia [59]. Molecular docking was used to screen the potential of each drug component for targeting a protein molecule.…”

“…They reported that fumigatoside E and aspergicin as introduced alkaloids were the most suitable active sites for ACE2, and they predicted a positive effect in preventing and eradicating SARS-CoV-2 infection that should be further studied. Syahputra et al screened secondary metabolites against SARS-CoV-2 isolated from 36 marine organisms with high biodiversity from Indonesia [59]. Molecular docking was used to screen the potential of each drug component for targeting a protein molecule.…”

“…They suggested that inhibiting the enzymatic activity of ACE2 could prevent spike proteins from binding to ACE2. Accordingly, among the marine derived natural products Syahputra et al screened secondary metabolites against SARS-CoV-2 isolated from 36 marine organisms with high biodiversity from Indonesia [59]. Molecular docking was used to screen the potential of each drug component for targeting a protein molecule.…”

The Potential of Indonesian Marine Natural Product With Dual Targeting Activity Through Sars-Cov-2 3clpro and Plpro: An in Silico Studies

“…These secondary metabolites from Indonesian marine invertebrates can be explored and investigated further regarding their biological activity and potential as an antiviral for Covid-19 treatment. Several types of marine invertebrates were also reported to inhibit important proteases of SARS-CoV-2 based on studies [11]. In addition to considering the side effects of drugs that are already available, the target for discovering new drug compounds is also quite important to support the success of drug action on Covid-19.…”