In-silico identification of novel natural drug leads against the Ebola virus VP40 protein: A promising approach for developing new antiviral therapeutics

Siddiquee, Noimul Hasan; Hossain, Md Ifteker; Talukder, Md Enamul Kabir; Nirob, Syed Afnan Arefin; Shourav, Md; Jahan, Israt; Tamanna, Umme Habiba Akter; Das, Pinky; Akter, Rahima; Hasan, Mahmudul; Abdullah-Al-Mamun, Md; Saha, Otun

doi:10.1016/j.imu.2024.101458

Cited by 5 publications

(1 citation statement)

References 46 publications

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“…To keep the salt concentration at 0.15 M, Cl– and Na+ ions were selected and filled randomly in the solvated method. 43 The OPLS3e force field mitigated and relaxed the system. 35 At last, the constant pressure-constant temperature (NPT) ensemble was executed at 1.01325 bar pressure and 300.0 K temperature.…”

Section: Methodsmentioning

confidence: 99%

Antiviral Activity, Pharmacoinformatics, Molecular Docking, and Dynamics Studies of Azadirachta indica Against Nipah Virus by Targeting Envelope Glycoprotein: Emerging Strategies for Developing Antiviral Treatment

Saha,

Siddiquee,

Akter

et al. 2024

Bioinform Biol Insights

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The Nipah virus (NiV) belongs to the Henipavirus genus is a serious public health concern causing numerous outbreaks with higher fatality rate. Unfortunately, there is no effective medication available for NiV. To investigate possible inhibitors of NiV infection, we used in silico techniques to discover treatment candidates in this work. As there are not any approved treatments for NiV infection, the NiV-enveloped attachment glycoprotein was set as target for our study, which is responsible for binding to and entering host cells. Our in silico drug design approach included molecular docking, post-docking molecular mechanism generalised born surface area (MM-GBSA), absorption, distribution, metabolism, excretion/toxicity (ADME/T), and molecular dynamics (MD) simulations. We retrieved 418 phytochemicals associated with the neem plant ( Azadirachta indica) from the IMPPAT database, and molecular docking was used to ascertain the compounds’ binding strength. The top 3 phytochemicals with binding affinities of −7.118, –7.074, and −6.894 kcal/mol for CIDs 5280343, 9064, and 5280863, respectively, were selected for additional study based on molecular docking. The post-docking MM-GBSA of those 3 compounds was −47.56, –47.3, and −43.15 kcal/mol, respectively. As evidence of their efficacy and safety, all the chosen drugs had favorable toxicological and pharmacokinetic (Pk) qualities. We also performed MD simulations to confirm the stability of the ligand-protein complex structures and determine whether the selected compounds are stable at the protein binding site. All 3 phytochemicals, Quercetin (CID: 5280343), Cianidanol (CID: 9064), and Kaempferol (CID: 5280863), appeared to have outstanding binding stability to the target protein than control ribavirin, according to the molecular docking, MM-GBSA, and MD simulation outcomes. Overall, this work offers a viable approach to developing novel medications for treating NiV infection.

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Section: Methodsmentioning

confidence: 99%