Glycan-dependent chikungunya viral infection divulged by antiviral activity of NAG specific chi-like lectin

Kaur, Ramanjit; Neetu, .; Mudgal, Rajat; Jose, Joyce; Kumar, Pravindra; Tomar, Shailly

doi:10.1016/j.virol.2018.10.009

Cited by 36 publications

(30 citation statements)

References 61 publications

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“…RNA viruses like chikungunya virus, dengue virus, Ebola virus, SARS, MERS, Sindbis virus etc. can thus be targeted at each of these steps of their life cycle to combat infections caused by them (39). Antiviral drugs blocking entry of virus or acting on replication stages have been reported against dengue, chikungunya virus and other similar RNA viruses (40,41).…”

Section: Discussionmentioning

confidence: 99%

Identification of SARS-CoV-2 Cell Entry Inhibitors by Drug Repurposing Using in silico Structure-Based Virtual Screening Approach

2020

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The rapidly spreading, highly contagious and pathogenic SARS-coronavirus 2 (SARS-CoV-2) associated Coronavirus Disease 2019 (COVID-19) has been declared as a pandemic by the World Health Organization (WHO). The novel 2019 SARS-CoV-2 enters the host cell by binding of the viral surface spike glycoprotein (S-protein) to cellular angiotensin converting enzyme 2 (ACE2) receptor. The virus specific molecular interaction with the host cell represents a promising therapeutic target for identifying SARS-CoV-2 antiviral drugs. The repurposing of drugs can provide a rapid and potential cure toward exponentially expanding COVID-19. Thereto, high throughput virtual screening approach was used to investigate FDA approved LOPAC library drugs against both the receptor binding domain of spike protein (S-RBD) and ACE2 host cell receptor. Primary screening identified a few promising molecules for both the targets, which were further analyzed in details by their binding energy, binding modes through molecular docking, dynamics and simulations. Evidently, GR 127935 hydrochloride hydrate, GNF-5, RS504393, TNP, and eptifibatide acetate were found binding to virus binding motifs of ACE2 receptor. Additionally, KT203, BMS195614, KT185, RS504393, and GSK1838705A were identified to bind at the receptor binding site on the viral S-protein. These identified molecules may effectively assist in controlling the rapid spread of SARS-CoV-2 by not only potentially inhibiting the virus at entry step but are also hypothesized to act as anti-inflammatory agents, which could impart relief in lung inflammation. Timely identification and determination of an effective drug to combat and tranquilize the COVID-19 global crisis is the utmost need of hour. Further, prompt in vivo testing to validate the anti-SARS-CoV-2 inhibition efficiency by these molecules could save lives is justified.

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Section: Discussionmentioning

confidence: 99%

Identification of SARS-CoV-2 Cell Entry Inhibitors by Drug Repurposing Using in silico Structure-Based Virtual Screening Approach

2020

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“…In the second phase, it is fused with the host cell membrane and viral genetic material (RNA) is transferred into the host cell, (in next stage) later on, the viral genetic material gets a hold of host genome and start making structural and non-structural proteins and finally the viral parts are assembled and phages are ejaculated from host cell that are ready to attack other host cells [ 19 , 68 ]. In order to cure the infections caused by RNA viruses such as dengue virus, chikungunya virus, SARS, Ebola virus, Sindbis virus MERS, etc., it is necessary to target these viruses at any of the stage of their life cycle [ 19 , 69 ]. The drugs that block the entry of the virus into the host cell or inhibit the viral replication have already been introduced in the market for chikungunya, dengue, and other RNA viruses [ 19 , 70 ].…”

Section: Discussionmentioning

confidence: 99%

Promising terpenes as SARS-CoV-2 spike receptor-binding domain (RBD) attachment inhibitors to the human ACE2 receptor: Integrated computational approach

Muhseen

Hameed

Al-Hasani

et al. 2020

Journal of Molecular Liquids

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The spike protein receptor binding domain (S-RBD) is a necessary corona-viral protein for binding and entry of coronaviruses (COVs) into the host cells. Hence, it has emerged as an attractive antiviral drug target. Therefore, present study was aimed to target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S-RBD with novel bioactive compounds to retrieve potential candidates that could serve as anti-coronavirus disease 2019 (COVID-19) drugs. In this paper, computational approaches were employed, especially the structure-based virtual screening followed by molecular dynamics (MD) simulation as well as binding energy analysis for the computational identification of specific terpenes from the medicinal plants, which can block SARS-CoV-2 S-RBD binding to Human angiotensin-converting enzyme 2 (H-ACE2) and can act as potent anti-COVID-19 drugs after further advancements. The screening of focused terpenes inhibitors database composed of ~1000 compounds with reported therapeutic potential resulted in the identification of three candidate compounds, NPACT01552, NPACT01557 and NPACT00631. These three compounds established conserved interactions, which were further explored through all-atom MD simulations, free energy calculations, and a residual energy contribution estimated by MM-PB( GB )SA method. All these compounds showed stable conformation and interacted well with the hot-spot residues of SARS-CoV-2 S-RBD. Conclusively, the reported SARS-CoV-2 S-RBD specific terpenes could serve as seeds for developing potent anti-COVID-19 drugs. Importantly, the experimentally tested glycyrrhizin (NPACT00631) against SARS-CoV could be used further in the fast-track drug development process to help curb COVID-19.

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“…A recent clinical isolate of CHIKV (strain no. : 119067; GenBank: ) was propagated in Vero cells using standard viral adsorption techniques, quantified by standard plaque assays and stored at −80 °C . SAM, SAH, GTP, UMP, caffeine, sinefungin, ATA, and m 7 GTP were purchased from Sigma (St. Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Chikungunya virus by an adenosine analog targeting the SAM‐dependent nsP1 methyltransferase

2019

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Alphaviruses, including Chikungunya (CHIKV) and Venezuelan equine encephalitis virus (VEEV), are among the leading causes of recurrent epidemics all over the world. Alphaviral nonstructural protein 1 (nsP1) orchestrates the capping of nascent viral RNA via its S‐adenosyl methionine‐dependent N‐7‐methyltransferase (MTase) and guanylyltransferase activities. Here, we developed and validated a novel capillary electrophoresis (CE)‐based assay for measuring the MTase activity of purified VEEV and CHIKV nsP1. We employed the assay to assess the MTase inhibition efficiency of a few adenosine analogs and identified 5‐iodotubercidin (5‐IT) as an inhibitor of nsP1. The antiviral potency of 5‐IT was evaluated in vitro using a combination of cell‐based assays, which suggest that 5‐IT is efficacious against CHIKV in cell culture (EC50: 0.409 µm).

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Glycan-dependent chikungunya viral infection divulged by antiviral activity of NAG specific chi-like lectin

Cited by 36 publications

References 61 publications

Identification of SARS-CoV-2 Cell Entry Inhibitors by Drug Repurposing Using in silico Structure-Based Virtual Screening Approach

Identification of SARS-CoV-2 Cell Entry Inhibitors by Drug Repurposing Using in silico Structure-Based Virtual Screening Approach

Promising terpenes as SARS-CoV-2 spike receptor-binding domain (RBD) attachment inhibitors to the human ACE2 receptor: Integrated computational approach

Inhibition of Chikungunya virus by an adenosine analog targeting the SAM‐dependent nsP1 methyltransferase

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