Differences in pathogenicity among the mpox virus clades: impact on drug discovery and vaccine development

Andrei, Graciela; Snoeck, Robert

doi:10.1016/j.tips.2023.08.003

Cited by 3 publications

(2 citation statements)

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“…The B.1 lineage exhibits multiple mutations in genes associated with virulence, host recognition, and immune evasion. 61 In comparison to previously obtained complete genome sequences of Mpox virus isolated in Nigeria from 2017 to 2018, the Mpox virus strains that emerged in 2022 exhibited a higher number of single nucleotide polymorphisms (SNPs). The Mpox virus strain isolated in 2022 exhibit ~50 SNPs, indicating an approximately 6–12-fold increase in the predicted substitution rate of Mpox virus compared to the strains isolated from 2018-2019 (1–2 nucleotide substitutions per genome every year).…”

Section: Virus Morphology and Genomementioning

confidence: 97%

Mpox (formerly monkeypox): pathogenesis, prevention and treatment

Lu,

Xing,

Wang

et al. 2023

Sig Transduct Target Ther

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In 2022, a global outbreak of Mpox (formerly monkeypox) occurred in various countries across Europe and America and rapidly spread to more than 100 countries and regions. The World Health Organization declared the outbreak to be a public health emergency of international concern due to the rapid spread of the Mpox virus. Consequently, nations intensified their efforts to explore treatment strategies aimed at combating the infection and its dissemination. Nevertheless, the available therapeutic options for Mpox virus infection remain limited. So far, only a few numbers of antiviral compounds have been approved by regulatory authorities. Given the high mutability of the Mpox virus, certain mutant strains have shown resistance to existing pharmaceutical interventions. This highlights the urgent need to develop novel antiviral drugs that can combat both drug resistance and the potential threat of bioterrorism. Currently, there is a lack of comprehensive literature on the pathophysiology and treatment of Mpox. To address this issue, we conducted a review covering the physiological and pathological processes of Mpox infection, summarizing the latest progress of anti-Mpox drugs. Our analysis encompasses approved drugs currently employed in clinical settings, as well as newly identified small-molecule compounds and antibody drugs displaying potential antiviral efficacy against Mpox. Furthermore, we have gained valuable insights from the process of Mpox drug development, including strategies for repurposing drugs, the discovery of drug targets driven by artificial intelligence, and preclinical drug development. The purpose of this review is to provide readers with a comprehensive overview of the current knowledge on Mpox.

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Section: Virus Morphology and Genomementioning

confidence: 97%

Mpox (formerly monkeypox): pathogenesis, prevention and treatment

Lu,

Xing,

Wang

et al. 2023

Sig Transduct Target Ther

View full text Add to dashboard Cite

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“…Studies have focused mainly on the lethal Zaire strain (Clade I). The epidemiology, transmission, and pathology of the strains in Clade IIb are significantly different from those of the Zaire strain [ 17 ]. Concerning pathogenicity in humans, the Zaire strain is considered to be slightly more fatal than the other strains [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Mpox virus Clade IIb infected Cynomolgus macaques via mimic natural infection routes closely resembled human mpox infection

Li,

Chen,

Zhang

et al. 2024

Emerging Microbes & Infections

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Generating an infectious non-human primate (NHP) model using a prevalent monkeypox virus (MPXV) strain has emerged as a crucial strategy for assessing the efficacy of vaccines and antiviral drugs against human MPXV infection. Here, we established an animal model by infecting cynomolgus macaques with the prevalent MPXV strain, WIBP-MPXV-001, and simulating its natural routes of infection. A comprehensive analysis and evaluation were conducted on three animals, including monitoring clinical symptoms, collecting hematology data, measuring viral loads, evaluating cellular and humoral immune responses, and examining histopathology. Our findings revealed that initial skin lesions appeared at the inoculation sites and subsequently spread to the limbs and back, and all infected animals exhibited bilateral inguinal lymphadenopathy, eventually leading to a self-limiting disease course. Viral DNA was detected in post-infection blood, nasal, throat, rectal and blister fluid swabs. These observations indicate that the NHP model accurately reflects critical clinical features observed in human MPXV infection. Notably, the animals displayed clinical symptoms and disease progression similar to those of humans, rather than a lethal outcome as observed in previous studies. Historically, MPXV was utilized as a surrogate model for smallpox. However, our study contributes to a better understanding of the dynamics of current MPXV infections while providing a potential infectious NHP model for further evaluation of vaccines and antiviral drugs against mpox infection. Furthermore, the challenge model closely mimics the primary natural routes of transmission for human MPXV infections. This approach enhances our understanding of the precise mechanisms underlying the interhuman transmission of MPXV.

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