Molnupiravir: A lethal mutagenic drug against rapidly mutating severe acute respiratory syndrome coronavirus 2—A narrative review

Journal of Medical Virology, Год журнала: 2022, Номер 94(7), С. 3006 - 3016

Опубликована: Март 22, 2022

Broad-spectrum antiviral agents targeting viral RNA-dependent RNA polymerase (RdRp) are expected to be a key therapeutic strategy in the ongoing coronavirus disease 2019 (COVID-19) pandemic and its future variants of severe acute respiratory syndrome 2 (SARS-CoV-2), virus that causes COVID-19. Molnupiravir is nucleoside analog vivo experiments have been reported inhibit replication SARS-CoV-2, Clinical trials molnupiravir as therapy for patients with mild-to-moderate COVID-19 also suggest significant efficacy comparison placebo. lethally mutagenic against RNA, but effect on host cell DNA being questioned. Herein, safety concerns discussed recent findings from published reports clinical trials. The unchanged mutated SARS-CoV-2 highlighted. With administration via oral route, turn tide pandemic.

Язык: Английский

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In vitro and computational insights revealing the potential inhibitory effect of Tanshinone IIA against influenza A virus

Computers in Biology and Medicine, Год журнала: 2021, Номер 141, С. 105149 - 105149

Опубликована: Дек. 17, 2021

Язык: Английский

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Newly synthesized series of oxoindole–oxadiazole conjugates as potential anti-SARS-CoV-2 agents:in silicoandin vitrostudies

New Journal of Chemistry, Год журнала: 2022, Номер 46(11), С. 5078 - 5090

Опубликована: Янв. 1, 2022

The pharmacophoric features of the novel series 1,3,4-oxadiazole–oxoindole conjugates (IVa–g) as potential anti-SARS-CoV-2 agents based on reported M pro inhibitor (Ia) are presented.

Язык: Английский

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Anticoagulants as Potential SARS-CoV-2 Mpro Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR Studies

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(20), С. 12235 - 12235

Опубликована: Окт. 13, 2022

In this article, 34 anticoagulant drugs were screened in silico against the main protease (Mpro) of SARS-CoV-2 using molecular docking tools. Idraparinux, fondaparinux, eptifibatide, heparin, and ticagrelor demonstrated highest binding affinities towards Mpro. A dynamics study at 200 ns was also carried out for most promising anticoagulants to provide insights into dynamic thermodynamic properties compounds. Moreover, a quantum mechanical conducted which helped us attest some findings. biological evaluation (in vitro) compounds performed by carrying MTT cytotoxicity assay crystal violet order assess inhibitory concentration 50 (IC50). It is worth noting that displayed intrinsic potential inhibition with an IC50 value 5.60 µM safety index 25.33. addition, fondaparinux sodium dabigatran showed activities values 8.60 9.40 µM, respectively, indexes 17.60 15.10, respectively. Mpro enzyme investigated utilizing tipranavir as reference standard. Interestingly, attained 2.36 surpassing (IC50 = 7.38 µM) more than three-fold. Furthermore, highly eligible 10.59 µM. Finally, SAR discussed, counting on findings both vitro approaches.

Язык: Английский

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A Systematic Review of the Global Intervention for SARS-CoV-2 Combating: From Drugs Repurposing to Molnupiravir Approval

Drug Design Development and Therapy, Год журнала: 2022, Номер Volume 16, С. 685 - 715

Опубликована: Март 1, 2022

Abstract: The rising outbreak of SARS-CoV-2 continues to unfold all over the world. development novel effective antiviral drugs fight against is a time cost. As result, some specific FDA-approved have already been repurposed and authorized for COVID-19 treatment. used were either or non-antiviral drugs. Accordingly, present review thoroughly focuses on repurposing efficacy these including clinical trials experienced, combination therapies used, methods followed treatment, their future perspective. Therefore, drug was regarded as an avenue Recently, molnupiravir prodrug medication that approved in United Kingdom November 2021 treatment COVID-19. On other hand, PF-07321332 oral developed by Pfizer. For COVID-19, PF-07321332/ritonavir Phase III studies marketed Paxlovid. Herein, we represented almost history combating from recently available anti-SARS-CoV-2 candidates, new hope end current pandemic. Graphical Keywords: SARS-CoV-2, repurposing, trials, molnupiravir, paxlovid

Язык: Английский

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Bioactive Azadirachta indica and Melia azedarach leaves extracts with anti-SARS-CoV-2 and antibacterial activities

PLoS ONE, Год журнала: 2023, Номер 18(3), С. e0282729 - e0282729

Опубликована: Март 8, 2023

The leaves of Azadirachta indica L. and Melia azedarach L., belonging to Meliaceae family, have been shown medicinal benefits are extensively employed in traditional folk medicine. Herein, HPLC analysis the ethyl acetate fraction total methanolic extract emphasized enrichment both A . M extracts with phenolic flavonoids composites, respectively. Besides, 4 limonoids 2 were isolated using column chromatography. By assessing vitro antiviral activities against Severe Acute Respiratory Syndrome Corona virus (SARS-CoV-2), it was found that robust anti-SARS-CoV-2 at low half-maximal inhibitory concentrations (IC 50 ) 8.451 6.922 μg/mL, Due high safety cytotoxic (CC 446.2 351.4 μg/ml, respectively, displayed extraordinary selectivity indices (SI>50). could induce antibacterial Gram-negative positive bacterial strains. minimal varied from 25 100 mg/mL within 30 min contact time towards tested bacteria. Our findings confirm broad-spectrum value extracts. Finally, additional vivo investigations highly recommended anti-COVID-19 antimicrobial plant

Язык: Английский

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Zoonosis and zooanthroponosis of emerging respiratory viruses

Frontiers in Cellular and Infection Microbiology, Год журнала: 2024, Номер 13

Опубликована: Янв. 5, 2024

Lung infections in Influenza-Like Illness (ILI) are triggered by a variety of respiratory viruses. All human pandemics have been caused the members two major virus families, namely Orthomyxoviridae (influenza A viruses (IAVs); subtypes H1N1, H2N2, and H3N2) Coronaviridae (severe acute syndrome coronavirus 2, SARS−CoV−2). These acquired some adaptive changes known intermediate host including domestic birds (IAVs) or unknown (SARS-CoV-2) following transmission from their natural reservoirs (e.g. migratory bats, respectively). Verily, these substitutions facilitated crossing species barriers to infect humans phenomenon that is as zoonosis. Besides, aided variant strain transmit horizontally other contact non-human animal pets wild animals (zooanthroponosis). Herein we discuss main zoonotic reverse-zoonosis events occurred during last influenza A/H1N1 SARS-CoV-2. We also highlight impact interspecies pandemic on evolution possible prophylactic therapeutic interventions. Based information available presented this review article, it important close monitoring viral zoonosis reverse strains within One-Health One-World approach mitigate unforeseen risks, such resistance limited

Язык: Английский

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Ligand-based design, synthesis, computational insights, andin vitrostudies of novelN-(5-Nitrothiazol-2-yl)-carboxamido derivatives as potent inhibitors of SARS-CoV-2 main protease

Journal of Enzyme Inhibition and Medicinal Chemistry, Год журнала: 2022, Номер 37(1), С. 2112 - 2132

Опубликована: Июль 31, 2022

The global outbreak of the COVID-19 pandemic provokes scientists to make a prompt development new effective therapeutic interventions for battle against SARS-CoV-2. A series

Язык: Английский

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Investigating the possible mechanisms of pirfenidone to be targeted as a promising anti-inflammatory, anti-fibrotic, anti-oxidant, anti-apoptotic, anti-tumor, and/or anti-SARS-CoV-2

Life Sciences, Год журнала: 2022, Номер 309, С. 121048 - 121048

Опубликована: Окт. 7, 2022

Язык: Английский

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Identification of Natural Lead Compounds against Hemagglutinin-Esterase Surface Glycoprotein in Human Coronaviruses Investigated via MD Simulation, Principal Component Analysis, Cross-Correlation, H-Bond Plot and MMGBSA

Biomedicines, Год журнала: 2023, Номер 11(3), С. 793 - 793

Опубликована: Март 6, 2023

The pandemic outbreak of human coronavirus is a global health concern that affects people all ages and genders, but there currently still no effective, approved potential drug against coronavirus, as many other vaccines have serious side effects while the development small antiviral inhibitors has gained tremendous attention. For this research, HE was used therapeutic target, spike protein displays high binding affinity for both host ACE2 viral glycoprotein. Molecular docking, pharmacophore modelling virtual screening 38,000 natural compounds were employed to find out best inhibitor coronaviruses with more efficiency fewer further evaluated via MD simulation, PCA, DCCR MMGBSA. lead compound 'Calceolarioside B' identified on basis pharmacophoric features which depict favorable (ΔGbind -37.6799 kcal/mol) HE(5N11) receptor describes positive correlation movements in active site residues better stability, robust H-bond network, compactness reliable ADMET properties. Fraxinus sieboldiana Blume plant containing Calceolarioside B could be shows higher efficacy potency effects. This research work will aid investigators testing identification chemicals are effective useful coronavirus.

Язык: Английский

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