Antiviral Treatment against Monkeypox: A Scoping Review

Tropical Medicine and Infectious Disease, Journal Year: 2022, Volume and Issue: 7(11), P. 369 - 369

Published: Nov. 10, 2022

During the COVID-19 pandemic, increase in reports of human monkeypox virus infection cases spreading many countries outside Africa is a major cause for concern. Therefore, this study aimed to explore evidence antiviral pharmacotherapy available treatment adult patients with monkeypox. A scoping review literature was conducted using PubMed, Scopus, Web Science, Embase, and CENTRAL databases until 12 September 2022. The key search terms used were "monkeypox" "treatment". total 1927 articles retrieved strategy. After removing duplicates (n = 1007) examining by title, abstract, full text, 11 studies reporting case included, detailing number cases, clinical manifestations, participants treatment, history sexually transmitted diseases, method diagnosis, location skin lesions, drugs route administration, outcome. 1281 confirmed have been reported, which 65 had distributed most frequently United States 30), Kingdom 6), Spain 6). Of 1269 (99.1%) male an age range 18 76 years, 1226 (95.7%) sexual behavior being men who sex men. All diagnosed reverse transcriptase polymerase chain reaction (RT-PCR). frequent manifestations fever, lymphadenopathy, headache, fatigue, myalgia. locations lesions perianal, genital, facial, upper lower extremities. commonly were: tecovirimat, cidofovir, brincidofovir. complete recovery. According current evidence, efficacy safety against low quality scarce.

Language: Английский

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Exploration of Microbially Derived Natural Compounds against Monkeypox Virus as Viral Core Cysteine Proteinase Inhibitors

Viruses, Journal Year: 2023, Volume and Issue: 15(1), P. 251 - 251

Published: Jan. 16, 2023

Monkeypox virus (MPXV) is a member of the

Language: Английский

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Computer-assisted drug repurposing for thymidylate kinase drug target in monkeypox virus

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: May 29, 2023

Introduction Monkeypox is a zoonotic disease caused by brick-shaped enveloped monkeypox (Mpox) virus that belongs to the family of ancient viruses known as Poxviridae. Subsequently, have been reported in various countries. The transmitted respiratory droplets, skin lesions, and infected body fluids. patients experience fluid-filled blisters, maculopapular rash, myalgia, fever. Due lack effective drugs or vaccines, there need identify most potent reduce spread monkeypox. current study aimed use computational methods quickly potentially against Mpox virus. Methods In our study, protein thymidylate kinase (A48R) was targeted because it unique drug target. We screened library 9000 FDA-approved compounds DrugBank database using silico approaches, such molecular docking dynamic (MD) simulation. Results Based on score interaction analysis, DB12380, DB13276, DB11740, DB14675, DB11978, DB08526, DB06573, DB15796, DB08223, DB11736, DB16250, DB16335 were predicted potent. To examine behavior stability docked complexes, three compounds—DB16335, DB16250 —along with Apo state simulated for 300ns. results revealed compound best (-9.57 kcal/mol) kinase. Discussion Additionally, during 300 ns MD simulation period, showed great stability. Further, vitro vivo recommended final compounds.

Language: Английский

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An overview on monkeypox virus: Pathogenesis, transmission, host interaction and therapeutics

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Feb. 10, 2023

Orthopoxvirus is one of the most notorious genus amongst Poxviridae family. Monkeypox (MP) a zoonotic disease that has been spreading throughout Africa. The spread global, and incidence rates are increasing daily. virus rapid due to human-to-human animals-to-human transmission. World Health Organization (WHO) declared monkeypox (MPV) as global health emergency. Since treatment options limited, it essential know modes transmission symptoms stop spread. information from host–virus interactions revealed significantly expressed genes important for progression MP infection. In this review, we highlighted structure, modes, available therapeutic options. Furthermore, review provides insights scientific community extend their research work in field.

Language: Английский

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Identification and Investigation of a Cryptic Binding Pocket of the P37 Envelope Protein of Monkeypox Virus by Molecular Dynamics Simulations

The Journal of Physical Chemistry Letters, Journal Year: 2023, Volume and Issue: 14(13), P. 3230 - 3235

Published: March 27, 2023

The spread of the monkeypox virus has surged during unchecked COVID-19 epidemic. most crucial target is viral envelope protein, p37. However, lacking p37's crystal structure a significant hurdle to rapid therapeutic discovery and mechanism elucidation. Structural modeling molecular dynamics (MD) enzyme with inhibitors reveal cryptic pocket occluded in unbound structure. For first time, inhibitor's dynamic flip from active site enlightens allosteric site, which squeezes impairing its function. A large force needed for inhibitor dissociation ushering biological importance. In addition, hot spot residues identified at both locations discovered drugs more potent than tecovirimat may enable even robust designs against p37 accelerate development therapies.

Language: Английский

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Drug repurposing for Mpox: Discovery of small molecules as potential inhibitors against DNA‐dependent RNA polymerase using molecular modeling approach

Journal of Cellular Biochemistry, Journal Year: 2023, Volume and Issue: 124(5), P. 701 - 715

Published: March 22, 2023

Mpox (formerly Monkeypox), a zoonotic illness caused by the virus, belongs to Orthopoxvirus genus in family Poxviridae. To design and develop effective antiviral therapeutics against DNA viruses, DNA-dependent RNA polymerase (DdRp) of poxviruses has emerged as promising drug target. In present study, we modeled three-dimensional (3D) structure DdRp using template-based homology approach. After modeling, virtual screening was performed probe molecular interactions between 1755 Food Drug Administration-approved small molecule drugs (≤500 weight) Mpox. Based on binding affinity interaction patterns, five drugs, lumacaftor (-11.7 kcal/mol), conivaptan betulinic acid (-11.6 fluspirilene (-11.3 imatinib (-11.2 have been ranked top compounds interacting with DdRp. Complexes these shortlisted were further evaluated state-of-the-art all-atoms dynamics (MD) simulations 200 nanoseconds followed principal component analysis (PCA). MD PCA results revealed highly stable due validation wet-lab available vitro vivo experiments, repurposed can be utilized for treatment contagious virus. The outcome this study may establish solid foundation screen natural potential different pathogenic viruses.

Language: Английский

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A multi-targeted computational drug discovery approach for repurposing tetracyclines against monkeypox virus

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Sept. 4, 2023

Monkeypox viral infection is an emerging threat and a major concern for the human population. The lack of drug molecules to treat this disease may worsen problem. Identifying potential targets can significantly improve process developing potent treating monkeypox. proteins responsible replication are attractive targets. inhibitors from known that target these be key finding cure In work, two proteins, DNA-dependent RNA polymerase (DdRp) core cysteine proteinase, were considered as Sixteen antibiotic drugs tetracycline class screened against both through high-throughput virtual screening. These have ability inhibit bacterial protein synthesis, which makes antibiotics prominent candidate repurposing. Based on screening result obtained DdRp, top compounds, namely Tigecycline Eravacycline with docking scores - 8.88 7.87 kcal/mol, respectively, selected further analysis. Omadacycline minocycline, 10.60 7.51 compounds after proteinase library. along reference GTP DdRp tecovirimat used form protein-ligand complexes, followed by their evaluation 300 ns molecular dynamic simulation. MM/GBSA binding free energy calculation principal components analysis complexes also conducted understanding stability affinity respective proteins. Overall, study demonstrates repurposing tetracycline-derived therapeutic solution monkeypox infection.

Language: Английский

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In silico discovery of potent inhibitors against monkeypox’s major structural proteins

Journal of Biomolecular Structure and Dynamics, Journal Year: 2023, Volume and Issue: 41(23), P. 14259 - 14274

Published: Feb. 25, 2023

Monkeypox virus (MPXV) outbreak in non-endemic countries is a worldwide public health emergency. An enveloped double-stranded DNA belongs to the genus Orth poxvirus. A viral zoonotic infection known as monkeypox has been serious risk health, especially Africa. However, it recently spread other continents, so might soon become problem. There an increased of transmission because there lack effective treatment that cures disease. To stop multi-country from spreading, important discover medications urgently. The objective current study swiftly find new treatments for using advanced computational approaches. By investigating five potential MPXV targets (DNA ligase, Palmytilated Extracellular Enveloped Virus (EEV) membrane protein, Scaffold protein D13, Thymidylate Kinase, and Viral core cysteine proteinase), this research was carried out cutting-edge techniques against human infection. Here we present accurate 3D structures their binding cavities selected with higher confidence AlphaFold 2 SiteMap analysis. Molecular docking MD simulation analysis revealed top lead compounds affinity stability toward targets. Binding free energy calculations essential dynamics supports finding. utilizing virtual screening drug repurposing approach reported are beneficial medical scientists experimental biologists development MPXV.

Language: Английский

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Antivirals against Monkeypox (Mpox) in Humans: An Updated Narrative Review

Life, Journal Year: 2023, Volume and Issue: 13(10), P. 1969 - 1969

Published: Sept. 26, 2023

As of 29 August 2023, a total 89,596 confirmed cases Mpox (monkeypox) have been documented across 114 countries worldwide, with 157 reported fatalities. The outbreak that transpired in 2022 predominantly affected young men who sex (MSM). While most exhibited mild clinical course, individuals compromised immune systems, particularly those living HIV infection and possessing CD4 count below 200 cells/mm3, experienced more severe trajectory marked by heightened morbidity mortality. approach to managing is primarily symptomatic supportive. However, instances characterized or complicated manifestations, the utilization antiviral medications becomes necessary. Despite tecovirimat’s lack official approval FDA for treating humans, wealth positive experiences exists, pending outcomes ongoing trials. Brincidofovir cidofovir also administered select due unavailability tecovirimat. Within scope this narrative review, our objective was delve into attributes explore observational studies shed light on these agents.

Language: Английский

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Update on monkeypox virus infection: Focusing current treatment and prevention approaches

Fundamental and Clinical Pharmacology, Journal Year: 2024, Volume and Issue: 38(3), P. 465 - 478

Published: Jan. 16, 2024

Abstract Background While the world is still facing global pandemic COVID‐19, another zoonosis monkeypox (Mpox) has emerged posing a great threat to society. Insight into pathogenesis, symptoms, and management strategies will aid in development of potent therapeutics for treatment virus infection. Objectives To get insight current prevention effectively coping with disease. Methods For obtaining information regarding ongoing drugs under pipeline, we referred Google Scholar, Pub Med, Chem, WHO official site. Results There are few that came out be effective Mpox. Tecovirimat acts by inhibiting viral replication wrapping. Another drug cidofovir, which hinders activity DNA polymerase but drawback nephrotoxicity. overcome this, conjugate cidofovir being used—known as brincidofovir—which similar mechanism lesser toxicity. Ribavirin via inosine monophosphate dehydrogenase (IMPDPH) thus disrupting translation. It also interferes helicase activity. Tiazofurin, Adenosine N1 oxide, HPMPA have shown efficacy in‐vitro studies IMPDH, polymerase, mRNA translation respectively. In‐silico proven effect nilotinib, simeprevir, dihydroergotamine Mpox treatment. They binding affinity proteins required growth release MPXV. Vaccines been employed Mpox, includes JYNNEOS, ACAM2000, VIGIV. Conclusion This review highlights pathogenesis virus, disease manifestations, drugs, vaccines used those pipeline

Language: Английский

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