In silico ADMET and molecular docking study on searching potential inhibitors from limonoids and triterpenoids for COVID-19

Abstract

Virtual screening of phytochemicals was performed through molecular docking, simulations, in silico ADMET and drug-likeness prediction to identify the potential hits that can inhibit the effects of SARS-CoV-2. Considering the published literature on medicinal importance, 154 phytochemicals with analogous structure from limonoids and triterpenoids were selected to search potential inhibitors for the five therapeutic protein targets of SARS-CoV-2, i.e., 3CLpro (main protease), PLpro (papain-like protease), SGp-RBD (spike glycoprotein-receptor binding domain), RdRp (RNA dependent RNA polymerase) and ACE2 (angiotensin-converting enzyme 2). The in silico computational results revealed that the phytochemicals such as glycyrrhizic acid, limonin, 7-deacetyl-7-benzoylgedunin, maslinic acid, corosolic acid, obacunone and ursolic acid were found to be effective against the target proteins of SARS-CoV-2. The protein-ligand interaction study revealed that these phytochemicals bind with the amino acid residues at the active site of the target proteins. Therefore, the core structure of these potential hits can be used for further lead optimization to design drugs for SARS-CoV-2. Also, the medicinal plants containing these phytochemicals like licorice, neem, tulsi, citrus and olives can be used to formulate suitable therapeutic approaches in traditional medicines.

Chinese herbal medicine: Fighting SARS-CoV-2 infection on all fronts

“…Furthermore, GA has been evaluated by many groups for its ability to inhibit infections to multiple viruses in vitro and in humans, including SARS-CoV (EC 50 = 365 μM in Vero cells with an SI > 65) ( Hoever et al, 2005 ), HIV (90% inhibition of HIV replication in 60% patients) ( Sasaki et al, 2002 ), Epstein-Barr virus ( Lin et al, 2008 ), and varicella-zoster virus (the 50% infectious dose was 710 μM with an SI = 30) ( Baba et al, 1987 ). Multiple lines of evidence ( Bailly et al, 2020 ; Sinha et al, 2020 ; Li et al, 2020d ; Vardhan et al, 2020 ; Ray et al, 2020 ) now support the critical role of for the treatment of SARS-CoV-2 infection. Krawczyk et al revealed that GA could effectively inhibit the replication of SARS-CoV-2 M pro in Vero E6 cells at an EC 50 of 0.44 mg/ml in vitro ( Sand et al, 2020 ).…”

Essential interpretations of bioinformatics in COVID-19 pandemic

“…Metagenomics applications have also introduced in recent COVID-19 pandemics to reveal some critical novel information regarding SARS-CoV-2. The metagenomics has been used for rapid identification and quick characterization of the first few cases of COVID19 ( Chen et al, 2020 ; Manning et al, 2020 ), for examining the SARS-CoV-2 with other co-infections in nasopharyngeal throat swabs of patients ( Vardhan and Sahoo, 2020 ), identification of the intermediate host in transferring the infection to human body ( Lam et al, 2020 ), screening of the homologous sequence of SARS-CoV-2 in other organisms ( Wahba et al, 2020 ), the effect of SARS-CoV-2 in human faecal microbiome alterations ( Zuo et al, 2020 ), clinical SARS-CoV-2 infection with bacterial co-infections ( Peddu et al, 2020 ) etc. These findings have helped and are helping, the clinicians for better isolation of COVID-19 patients with different symptoms ( Table 1 ).…”

“…The potentiality of CADD has been exploited to the fullest in finding a solution for this COVID-19 outbreak. Researchers have taken the privilege of CADD including structure-based drug design, network-based drug design towards the identification of potential drug candidates against the identified viral proteins including Spike (S) protein ( Prasanth et al, 2020 ; Hall Jr and Ji, 2020 ; Wei et al, 2020 ; Fantini et al, 2020 ; BR et al, 2020 ; Cavasotto and Di Filippo, 2020 ; Vardhan and Sahoo, 2020 ; Panda et al, 2020 ), Nucleocapsid (N) protein ( Sarma et al, 2020 ; Ray et al, 2020a ; Bhowmik et al, 2020 ; Lavecchia and Fernandez, 2020 ), Envelop protein ( Bhowmik et al, 2020 ; Lavecchia and Fernandez, 2020 ; Gupta et al, 2020 ), Membrane (M) Protein ( Bhowmik et al, 2020 ), Main protease (M pro) ( Prasanth et al, 2020 ; Cavasotto and Di Filippo, 2020 ; Vardhan and Sahoo, 2020 ; Panda et al, 2020 ; Kumar et al, 2020 ), 3CL protease ( Hall Jr and Ji, 2020 ; Vardhan and Sahoo, 2020 ; Jo et al, 2020 ) of SARS-CoV-2 by using the bioinformatics tools and software ( Table 6 ). This immediate and effective action has not only predicted novel putative natural inhibitors but also re-experimented some previously used ancient synthetic drugs with antiviral activities like chloroquine (malaria), hydroxylchloroquine (maalaria), zanamivir (influenza A & B virus), indinavir (HIV), saquinavir (HIV), remdesivir (SARS-CoV), ralterravin (HIV), strptomycine, ciprofloxacin, zanamivir (influenza virus), glycyrrhizic acid (anti inflammation) etc.…”

Targeting Neurological Manifestations of Coronaviruses by Candidate Phytochemicals: A Mechanistic Approach

“…A study by Vardhan et al , showed that one hundred fifty-four analogous of limonoids and triterpenoids showed potential inhibitory effects on ACE2, 3CLpro, PLpro, spike protein, and RdRp. Another in silico study also showed that limonin, obacunone, ursolic acid, glycyrrhizic acid, 7-deacetyl-7-benzoylgedunin, maslinic acid, and corosolic acid effectively target SARS-CoV-2 proteins ( Vardhan and Sahoo, 2020 ).…”