The emergence of new lineages of the Mpox virus could affect the 2022 outbreak

Costa, Mayla Abrahim; Guterres, Alexandro; Neves, Patrícia Cristina da Costa; Bom, Ana Paula Dinis Ano

doi:10.1101/2022.07.07.498743

Cited by 12 publications

(11 citation statements)

References 31 publications

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“…A27L possesses a reverse open‐reading frame gene that encodes 1 of the viral A‐type inclusion proteins frequently targeted for viral neutralization 53 and is responsible for environmental protection during Orthopoxvirus infections 54 . Meanwhile, MP2 was positioned inside the gene A50R that encodes the ATP‐dependent DNA ligase, responsible for repairing nicked DNA duplexes in Vaccinia virus 55 with mutations associated in new lineages of MPXV isolates 56 . Furthermore, conservation studies analyzing disease‐related Orthopoxvirus genomes against MPXV G‐rich sequences showed that putative G4s are MPXV‐exclusive (Figure 1B).…”

Section: Discussionmentioning

confidence: 99%

Mapping and characterization of G‐quadruplexes in monkeypox genomes

Pereira

Gemmill

Siddiqui

et al. 2023

Journal of Medical Virology

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Monkeypox virus (MPXV) is a double-stranded DNA virus from the family Poxviridae, which is endemic in West and Central Africa. Various human outbreaks occurred in the 1980s, resulting from a cessation of smallpox vaccination. Recently, MPXV cases have reemerged in non-endemic nations, and the 2022 outbreak has been declared a public health emergency. Treatment optionsare limited, and many countries lack the infrastructure to provide symptomatic treatments. The development of cost-effective antivirals could ease severe health outcomes. G-quadruplexes have been a target of interest in treating viral infections with different chemicals. In the present work, a genomic-scale mapping of different MPXV isolates highlighted two conserved putative quadruplex-forming sequences MPXV-exclusive in 590 isolates.Subsequently, we assessed the G-quadruplex formation using circular dichroism spectroscopy and solution small-angle X-ray scattering. Furthermore, biochemical assays indicated the ability of MPXV quadruplexes to be recognized by two specific G4-binding partners-Thioflavin T and DHX36. Additionally, our work also suggests that a quadruplex binding small-molecule with previously reported antiviral activity, TMPyP4, interacts with MPXV G-quadruplexes with nanomolar affinity in the presence and absence of DHX36. Finally, cell biology experiments suggests that TMPyP4 treatment substantially reduced gene expression of MPXV proteins. In summary, our work provides insights into the G-quadruplexes from the MPXV genome that can be further exploited to develop therapeutics.

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Section: Discussionmentioning

confidence: 99%

Mapping and characterization of G‐quadruplexes in monkeypox genomes

Pereira

Gemmill

Siddiqui

et al. 2023

Journal of Medical Virology

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“…These alterations were shown to be microevolutionary. [55][56][57] Since 2017, the 2022 MPXV has been in circulation, even though it has a mutational bias consisting of approximately 50 SNPs, which may indicate the presence of APOBEC3 activity. The number of SNPs that have been observed is greater than what should be anticipated based on the known substitution rates of orthopoxviruses that have occurred in the past.…”

Section: Genomic Changes In the 2022 Mpxv Genomesmentioning

confidence: 99%

Human-to-Human Transmission of Monkeypox Virus Old Virus with a New Face

Joshi¹,

Loshali²,

Ale³

et al. 2022

J. Pure Appl. Microbiol.

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The outbreak of Monkeypox was declared a public health emergency of worldwide concern by WHO following the (COVID-19) pandemic. The number of reported cases of both suspicion and confirmation has increased in recent years, from over 19,000 between 2000 and 2019 to over 15,600 between 2021 and 2022, and day by day the cases of monkeypox have been reported in 12 member states to three WHO regions. As of May 21, 2022, 92 confirmed cases of monkeypox and 28 suspected cases had been reported to the WHO from more than 12 countries. By the 21st of June 2022, a total of 2677 confirmed cases had been recorded from the UK and other European and non-European countries. According to an extensive literature survey, the total number of registered cases of MPXV was 59,147 between January 2022 to September 14th, 2022, demonstrating that MPXV can spread significantly amongst people and may as a result pose a serious threat to public health with international repercussions. In clade II MPXV virus is currently occurring outside of Africa the WHO reported 25,047 confirmed cases as of August 2nd, 2022. Here, we review current better understanding, and studies on monkeypox, including its history, current scenario, epidemiology, causative agent, symptoms, diagnosis, treatment, limitations, and the new face of monkeypox, its unusual outbreak attributed to the transformation of transmission and also discussed case studies is discussed in this article.

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“…The Central African trait was more severe and transmissible than the West African trait but due to general viral evolution a third multi country outbreak strain has been reported that led to spread of disease all over the world. 5,6 Smallpox and monkeypox share somewhat same symptoms but monkeypox is less severe than smallpox. The same vaccination would have been effective against monkeypox but due to eradication of smallpox in 1980, the vaccine was discontinued.…”

Section: Introductionmentioning

confidence: 99%

Computational Purposing Phytochemicals against Cysteine Protease of Monkeypox Virus: An In-silico Approach

Bansal¹,

Gupta²,

Sangwan³

et al. 2022

J. Pure Appl. Microbiol.

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The development and evolution of viruses that cause disease have presented a formidable challenge to contemporary medicine and the global economy, not to mention a catastrophic risk to human health. Almost all of these viruses are zoonotic, meaning they were first identified in animals and then spread to humans. An emerging virus may cause only a few isolated instances, resulting in a limited outbreak, or it may cause widespread infection and spread to other parts of the world, triggering a full-blown epidemic. These kinds of emerging occurrences have occurred frequently and in many different forms during the past few decades. Monkeypox is a zoonotic disease caused by the monkeypox virus, a member of the orthopox family that also includes variola, cowpox, and vaccinia. Both animals and humans can get infected by this virus. Similar to smallpox this disease shows less severe rashes and lower mortality rate. The outbreak of monkeypox was declared a global public health emergency by the World Health Organization in July 2022. Unknown mutations and variations are linked to the recent epidemic. Presently, FDA approved tecovirimat, cidofovir and brincidofovir are there in market to treat monkeypox virus. But there are some side effects of these drugs as they are synthetic. So, scientists are working on natural remedies that can be used as alternative to these drugs. In the present study virtual screening of phytochemicals (N-(2-Allylcarbamoyl-4-chloro-phenyl)-3,4-dimethoxy-benzamide, 6-Dimethylaminonaphthene-1-sulfonicacid amide, Oleic Acid and dipentyl ester) from Allophylus serratus were employed against core viral cysteine proteases from monkeypox virus was done. The docking study revealed that selected ligands bind with target viral protein with binding affinity in the range of -5.0 to -6.7 kcal/mol. N-(2-Allylcarbamoyl-4-chloro-phenyl)-3,4-dimethoxy-benzamide showed the highest binding affinity of -6.7 kcal/mol which can be investigated in the future to design potential drugs against monkeypox virus. Thus, this study foresees the possibility of bioactive phytochemicals functioning as template molecules for further experimental evaluation of their efficiency against monkeypox virus.

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The emergence of new lineages of the Mpox virus could affect the 2022 outbreak

Cited by 12 publications

References 31 publications

Mapping and characterization of G‐quadruplexes in monkeypox genomes

Mapping and characterization of G‐quadruplexes in monkeypox genomes

Human-to-Human Transmission of Monkeypox Virus Old Virus with a New Face

Computational Purposing Phytochemicals against Cysteine Protease of Monkeypox Virus: An In-silico Approach

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