Monkeypox virus

Cho, C T; Wenner, Herbert A.

doi:10.1128/br.37.1.1-18.1973

Cited by 193 publications

(176 citation statements)

References 46 publications

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“…Despite being a DNA virus, MPXV spends its whole life cycle in the cytoplasm of infected cells. The MPXV genome encodes all of the proteins essential for viral DNA replication, transcription, virion assembly, and egress [16,17]. There are no approved vaccines or drugs to treat the human monkeypox virus until 2019.…”

Section: Introductionmentioning

confidence: 99%

Novel Multi Epitope-based Vaccine against Monkeypox Virus: Vaccinomic approach

Shantier¹,

Mustafa²,

Abdelmoneim³

et al. 2022

Preprint

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Background: While mankind is still dealing with the COVID-19 pandemic, on May 7, 2022, a case of monkeypox virus (MPXV) has been reported to the WHO. Monkeypox is a viral zoonotic disease with characteristics comparable to those seen in smallpox cases in the past. It has been a public health threat, particularly in Africa, but recently have been circulating the world, consequently, may become a global public health threat in a very short period. Thus, the current work was planned and then constructed a multi-epitope vaccine that can evoke an immunological response against MPXV utilizing cell surface-binding protein as a target in order to develop a novel vaccine that is both safe and almost free of side effects. Results: The proposed vaccine composed of 304 amino acids and was shown to be antigenic in Vaxijen server (0. 5311) and nonallergenic in AllerTop server. The 3D structure of the designed vaccine is predicted, refined and validated by various in silico tools to assess the stability of the vaccine. Moreover, solubility of the vaccine construct was found greater than the average solubility provided by protein-Sol server indicating the solubility of the vaccine construct. Moreover, the most promising epitopes bound to MHC I and MHC II alleles were found having good binding affinities with low energies ranging between ₋7.0 - ₋8.1kcal/mol. Conclusion: We conclude from our research that the cell surface-binding protein is one of the primary proteins involved in MPXV pathogenesis. The most promising epitopes were selected using a rigorous procedure and used for vaccine design. As a result, our study will aid in the development of appropriate therapeutics and prompt the development of future vaccines against MPXV, which could serve as an important milestone in the production of an antiviral vaccine against MPXV.

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Section: Introductionmentioning

confidence: 99%

Novel Multi Epitope-based Vaccine against Monkeypox Virus: Vaccinomic approach

Shantier¹,

Mustafa²,

Abdelmoneim³

et al. 2022

Preprint

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“…Levels of viremia were also similar between animals and groups. As the viremia phase is generally short and variable during OPXV infections (38,39), we missed the viremic period for some animals and observed viable virus only within the blood on 1 day for the majority of other animals (most often on day 5 p.i., although days 8, 11, and 14 were also observed) (Tables 2 to 5). Viral DNA in blood was detected for longer FIG 4 Viable virus was detected in necropsy samples from MPXV-challenged prairie dogs.…”

Section: Resultsmentioning

confidence: 99%

Pharmacokinetics and Efficacy of a Potential Smallpox Therapeutic, Brincidofovir, in a Lethal Monkeypox Virus Animal Model

Hutson

Kondas

Mauldin

et al. 2021

mSphere

128

121

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Smallpox, caused by Variola virus (VARV), was eradicated in 1980; however, VARV bioterrorist threats still exist, necessitating readily available therapeutics. Current preparedness activities recognize the importance of oral antivirals and recommend therapeutics with different mechanisms of action. Monkeypox virus (MPXV) is closely related to VARV, causing a highly similar clinical human disease, and can be used as a surrogate for smallpox antiviral testing. The prairie dog MPXV model has been characterized and used to study the efficacy of antipoxvirus therapeutics, including recently approved TPOXX (tecovirimat). Brincidofovir (BCV; CMX001) has shown antiviral activity against double-stranded DNA viruses, including poxviruses. To determine the exposure of BCV following oral administration to prairie dogs, a pharmacokinetics (PK) study was performed. Analysis of BCV plasma concentrations indicated variability, conceivably due to the outbred nature of the animals. To determine BCV efficacy in the MPXV prairie dog model, groups of animals were intranasally challenged with 9 × 105 plaque-forming units (PFU; 90% lethal dose [LD90]) of MPXV on inoculation day 0 (ID0). Animals were divided into groups based on the first day of BCV treatment relative to inoculation day (ID–1, ID0, or ID1). A trend in efficacy was noted dependent upon treatment initiation (57% on ID–1, 43% on ID0, and 29% on ID1) but was lower than demonstrated in other animal models. Analysis of the PK data indicated that BCV plasma exposure (maximum concentration [Cmax]) and the time of the last quantifiable concentration (AUClast) were lower than in other animal models administered the same doses, indicating that suboptimal BCV exposure may explain the lower protective effect on survival. IMPORTANCE Preparedness activities against highly transmissible viruses with high mortality rates have been highlighted during the ongoing coronavirus disease 2019 (COVID-19) pandemic. Smallpox, caused by variola virus (VARV) infection, is highly transmissible, with an estimated 30% mortality. Through an intensive vaccination campaign, smallpox was declared eradicated in 1980, and routine smallpox vaccination of individuals ceased. Today's current population has little/no immunity against VARV. If smallpox were to reemerge, the worldwide results would be devastating. Recent FDA approval of one smallpox antiviral (tecovirimat) was a successful step in biothreat preparedness; however, orthopoxviruses can become resistant to treatment, suggesting the need for multiple therapeutics. Our paper details the efficacy of the investigational smallpox drug brincidofovir in a monkeypox virus (MPXV) animal model. Since brincidofovir has not been tested in vivo against smallpox, studies with the related virus MPXV are critical in understanding whether it would be protective in the event of a smallpox outbreak.

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“…Prior investigators have not reported MCV (a molluscipoxvirus) or MCV DNA in the blood. However, orthopoxviruses circulate in PBMCs, rather than in plasma in nonhuman primates [14]. Because we detected MCV in 4 of 11 plasma specimens (36%) but in only 1 of 10 PBMC specimens (10%), MCV may circulate preferentially in the plasma in severely immunocompromised patients with disseminated MCV lesions.…”

Section: Discussionmentioning

confidence: 72%

Detection of Molluscum Contagiosum Virus (MCV) DNA in the Plasma of an Immunocompromised Patient and Possible Reduction of MCV DNA With CMX-001

Cohen¹,

Davila²,

Ali³

et al. 2012

The Journal of Infectious Diseases

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Molluscum contagiosum virus (MCV) is a poxvirus that causes localized papules in healthy persons. We evaluated a woman with severe immunodeficiency and disseminated MCV. During treatment with CMX-001, an antiviral with activity against other poxviruses, MCV DNA was detected in 20% of plasma samples. When the patient was not receiving CMX-001, MCV DNA was detected in 50% of samples. We also noted improvement in warts on her fingers during CMX-001 therapy. Although MCV is caused by direct inoculation of virus into skin in healthy persons, in a severely immunocompromised person MCV DNA was present in blood and may spread by viremia.

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Monkeypox virus

Cited by 193 publications

References 46 publications

Novel Multi Epitope-based Vaccine against Monkeypox Virus: Vaccinomic approach

Novel Multi Epitope-based Vaccine against Monkeypox Virus: Vaccinomic approach

Pharmacokinetics and Efficacy of a Potential Smallpox Therapeutic, Brincidofovir, in a Lethal Monkeypox Virus Animal Model

Detection of Molluscum Contagiosum Virus (MCV) DNA in the Plasma of an Immunocompromised Patient and Possible Reduction of MCV DNA With CMX-001

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