Molecular docking studies of chloroquine and its derivatives against P23^pro‐zbd domain of chikungunya virus: Implication in designing of novel therapeutic strategies

Abstract

The arthropod‐transmitted chikungunya virus has emerged as an epidemic menace that causes debilitating polyarthritis. With this life‐threatening impact on humans, the possible treatment requires to cure the viral infectivity. But, devoid of any vaccine against the chikungunya virus (CHIKV), there is a need to develop a novel chemotherapeutic strategy to treat this noxious infection. CHIKV carries highly compact P23pro‐zbd structure that possesses potential RNA‐binding surface domains which extremely influences the use of RNA template during genome replication at the time of infection and pathogenesis. Therefore, computational approaches were used to explore the novel small molecule inhibitors targeting P23pro‐zbd domain. The tertiary structure was modeled and optimized using in silico approaches. The results obtained from PROCHECK (93.1% residues in favored regions), ERRAT (87.480 overall model quality) and ProSA (Z‐score: −11.72) revealed the reliability of the proposed model. Interestingly, a previously reported inhibitor, chloroquine possesses good binding affinities with the target domain. In‐depth analysis revealed that chloroquine derivatives such as didesethyl chloroquine hydroxyacetamide, cletoquine, hydroxychloroquine exhibited a better binding affinity. Notably, MD simulation analysis exhibited that Thr1312, Ala1355, Ala1356, Asn1357, Asp1364, Val1366, Cys1367, Ala1401, Gly1403, Ser1443, Tyr1444, Gly1445, Asn1459, and Thr1463 residues are the key amino acid responsible for stable ligand‐protein interaction. The results obtained from this study provide new insights and advances the understanding to develop a new approach to consider effective and novel drug against chikungunya. However, a detailed in vivo study is required to explore its drug likeliness against this life‐threatening disease.

Action mechanism of Roman chamomile in the treatment of anxiety disorder based on network pharmacology

“…“Small Molecules” option was selected to pretreat the ligand, select the “Full Minimization” module to minimize the energy of small molecules followed “Libdock” to select the docking mode using default docking parameters. Results of the scoring function were analyzed (Jiahui et al, 2020; Kumar et al., 2019; Peng et al., 2018; Qin et al., 2016).…”

SARS-CoV-2: Immune Response Elicited by Infection and Development of Vaccines and Treatments

“…Previous data from in vitro studies showed that chloroquine can display an antiviral capacity against Chikungunya virus (CHIK) and SARS-CoV (177,206). Furthermore, chloroquine was shown to be able to inhibit the entry of SARS-CoV-2 into Vero E6 cells at concentrations that do not cause cytotoxic effects in vivo (168).…”

Coalition: Advocacy for prospective clinical trials to test the post-exposure potential of hydroxychloroquine against COVID-19

“…Hydroxychloroquine and chloroquine have demonstrated in vitro antiviral effectiveness against Herpes simplex virus type 1 (8), Zika (9,10), HIV (11), MERS (12), SARS-CoV (12), HCoV-OC43 (13), Chikungunya (14), Hepatitis C (15), and several other viruses (11,16). For coronavirus, some studies suggested, at least in vitro, some efficacy of chloroquine on the SARS-CoV virus (12,13) or MERS-CoV (17).…”