Discovery and Development of Monkeypox Disease Treatments

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Biomedicines biomedicines	4.7	3.7	2013	15.4 Days	CHF 2600	Submit
Journal of Clinical Medicine jcm	3.9	5.4	2012	17.9 Days	CHF 2600	Submit
Pathogens pathogens	3.7	5.1	2012	16.4 Days	CHF 2700	Submit
Vaccines vaccines	7.8	7.0	2013	19.2 Days	CHF 2700	Submit
Viruses viruses	4.7	7.1	2009	13.8 Days	CHF 2600	Submit

13 pages, 1780 KiB

Open AccessArticle

A Subunit Vaccine Candidate Composed of Mpox Virus A29L, M1R, A35R, and B6R Elicits Robust Immune Response in Mice

by Xuetao Yang, Xidan Yang, Shouwen Du, Congxia Hu, Xiu Yang, Xingyun Wang, Xing Hu, Nino Rcheulishvili, Peng George Wang and Jihui Lin

Vaccines 2023, 11(9), 1420; https://doi.org/10.3390/vaccines11091420 - 25 Aug 2023

Cited by 3 | Viewed by 1381

Abstract

With no specific antiviral drugs and preventive vaccines against Mpox virus (MPXV), the epidemic has led to the declaration of a Public Health Emergency of International Concern. As a developmental direction for new vaccines, studies of subunit vaccines based upon MPXV antigen proteins [...] Read more.

With no specific antiviral drugs and preventive vaccines against Mpox virus (MPXV), the epidemic has led to the declaration of a Public Health Emergency of International Concern. As a developmental direction for new vaccines, studies of subunit vaccines based upon MPXV antigen proteins are lacking. In this study, A29L, M1R, A35R, and B6R of MPXV were expressed and purified from a prokaryotic system. The four MPXV antigen proteins in combination were mixed with aluminum hydroxide or CpG7909 as adjuvant, and subsequently used to inoculate mice. The results of enzyme-linked immunosorbent assay (ELISA), flow cytometry analyses, and enzyme-linked immunospot (ELISPOT) assays indicated that A29L, M1R, A35R, and B6R elicited high-level antigen-specific antibodies and CD4⁺ T cells-based cellular immune response in mice. Moreover, the results of virus neutralization assays suggested that sera from the mice immunized with four proteins elicited high neutralizing activities against the vaccinia virus. Notably, the results of ELISA, ELISPOT, and virus neutralization assays also showed that the CpG7909 adjuvant was more effective in inducing an immune response compared with the aluminum adjuvant. In summary, this study offers valuable insights for further studies of subunit vaccine candidates for the prevention of MPXV and other orthomyxoviruses. Full article

(This article belongs to the Topic Discovery and Development of Monkeypox Disease Treatments)

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25 pages, 9186 KiB

Open AccessArticle

Repurposing Anti-Dengue Compounds against Monkeypox Virus Targeting Core Cysteine Protease

by Mohd Imran, Abida, Nawaf M. Alotaibi, Hamdy Khamees Thabet, Jamal Alhameedi Alruwaili, Lina Eltaib, Ahmed Alshehri, Ahad Amer Alsaiari, Mehnaz Kamal and Abdulmajeed Mohammed Abdullah Alshammari

Biomedicines 2023, 11(7), 2025; https://doi.org/10.3390/biomedicines11072025 - 18 Jul 2023

Cited by 2 | Viewed by 1246

Abstract

The monkeypox virus (MPXV) is an enveloped, double-stranded DNA virus belonging to the genus Orthopox viruses. In recent years, the virus has spread to countries where it was previously unknown, turning it into a worldwide emergency for public health. This study employs a [...] Read more.

The monkeypox virus (MPXV) is an enveloped, double-stranded DNA virus belonging to the genus Orthopox viruses. In recent years, the virus has spread to countries where it was previously unknown, turning it into a worldwide emergency for public health. This study employs a structural-based drug design approach to identify potential inhibitors for the core cysteine proteinase of MPXV. During the simulations, the study identified two potential inhibitors, compound CHEMBL32926 and compound CHEMBL4861364, demonstrating strong binding affinities and drug-like properties. Their docking scores with the target protein were −10.7 and −10.9 kcal/mol, respectively. This study used ensemble-based protein–ligand docking to account for the binding site conformation variability. By examining how the identified inhibitors interact with the protein, this research sheds light on the workings of the inhibitors’ mechanisms of action. Molecular dynamic simulations of protein–ligand complexes showed fluctuations from the initial docked pose, but they confirmed their binding throughout the simulation. The MMGBSA binding free energy calculations for CHEMBL32926 showed a binding free energy range of (−9.25 to −9.65) kcal/mol, while CHEMBL4861364 exhibited a range of (−41.66 to −31.47) kcal/mol. Later, analogues were searched for these compounds with 70% similarity criteria, and their IC₅₀ was predicted using pre-trained machine learning models. This resulted in identifying two similar compounds for each hit with comparable binding affinity for cysteine proteinase. This study’s structure-based drug design approach provides a promising strategy for identifying new drugs for treating MPXV infections. Full article

(This article belongs to the Topic Discovery and Development of Monkeypox Disease Treatments)

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19 pages, 2367 KiB

Open AccessReview

An Updated Review on Monkeypox Viral Disease: Emphasis on Genomic Diversity

by Ali A. Rabaan, Nada A. Alasiri, Mohammed Aljeldah, Abeer N. Alshukairiis, Zainab AlMusa, Wadha A. Alfouzan, Abdulmonem A. Abuzaid, Aref A. Alamri, Hani M. Al-Afghani, Nadira Al-baghli, Nawal Alqahtani, Nadia Al-baghli, Mashahed Y. Almoutawa, Maha Mahmoud Alawi, Mohammed Alabdullah, Neda A. Al Bati, Abdulmonem A. Alsaleh, Huseyin Tombuloglu, Kovy Arteaga-Livias, Tareq Al-Ahdal, Mohammed Garout and Mohd Imran Show full author list Hide full author list

Biomedicines 2023, 11(7), 1832; https://doi.org/10.3390/biomedicines11071832 - 26 Jun 2023

Cited by 5 | Viewed by 2332

Abstract

Monkeypox virus has remained the most virulent poxvirus since the elimination of smallpox approximately 41 years ago, with distribution mostly in Central and West Africa. Monkeypox (Mpox) in humans is a zoonotically transferred disease that results in a smallpox-like disease. It was first [...] Read more.

Monkeypox virus has remained the most virulent poxvirus since the elimination of smallpox approximately 41 years ago, with distribution mostly in Central and West Africa. Monkeypox (Mpox) in humans is a zoonotically transferred disease that results in a smallpox-like disease. It was first diagnosed in 1970 in the Democratic Republic of the Congo (DRC), and the disease has spread over West and Central Africa. The purpose of this review was to give an up-to-date, thorough, and timely overview on the genomic diversity and evolution of a re-emerging infectious disease. The genetic profile of Mpox may also be helpful in targeting new therapeutic options based on genes, mutations, and phylogeny. Mpox has become a major threat to global health security, necessitating a quick response by virologists, veterinarians, public health professionals, doctors, and researchers to create high-efficiency diagnostic tests, vaccinations, antivirals, and other infection control techniques. The emergence of epidemics outside of Africa emphasizes the disease’s global significance. Increased monitoring and identification of Mpox cases are critical tools for obtaining a better knowledge of the ever-changing epidemiology of this disease. Full article

(This article belongs to the Topic Discovery and Development of Monkeypox Disease Treatments)

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16 pages, 1175 KiB

Open AccessReview

A Comprehensive Review on Monkeypox Viral Disease with Potential Diagnostics and Therapeutic Options

by Ali A. Rabaan, Seham A. Al-Shwaikh, Wadha A. Alfouzan, Ali M. Al-Bahar, Mohammed Garout, Muhammad A. Halwani, Hawra Albayat, Norah B. Almutairi, Mohammed Alsaeed, Jeehan H. Alestad, Maha A. Al-Mozaini, Tala M. Al Ashgar, Sultan Alotaibi, Abdulmonem A. Abuzaid, Yahya Aldawood, Abdulmonem A. Alsaleh, Hani M. Al-Afghani, Jaffar A. Altowaileb, Abeer N. Alshukairi, Kovy Arteaga-Livias, Kirnpal Kaur Banga Singh and Mohd Imran Show full author list Hide full author list

Biomedicines 2023, 11(7), 1826; https://doi.org/10.3390/biomedicines11071826 - 26 Jun 2023

Cited by 2 | Viewed by 1592

Abstract

The purpose of this review is to give an up-to-date, thorough, and timely overview of monkeypox (Mpox), a severe infectious viral disease. Furthermore, this review provides an up-to-date treatment option for Mpox. The monkeypox virus (MPXV) has remained the most virulent poxvirus for [...] Read more.

The purpose of this review is to give an up-to-date, thorough, and timely overview of monkeypox (Mpox), a severe infectious viral disease. Furthermore, this review provides an up-to-date treatment option for Mpox. The monkeypox virus (MPXV) has remained the most virulent poxvirus for humans since the elimination of smallpox approximately 41 years ago, with distribution mainly in central and west Africa. Mpox in humans is a zoonotically transferred disease that results in symptoms like those of smallpox. It had spread throughout west and central Africa when it was first diagnosed in the Republic of Congo in 1970. Mpox has become a major threat to global health security, necessitating a quick response by virologists, veterinarians, public health professionals, doctors, and researchers to create high-efficiency diagnostic tests, vaccinations, antivirals, and other infection control techniques. The emergence of epidemics outside of Africa emphasizes the disease’s global significance. A better understanding of Mpox’s dynamic epidemiology may be attained by increased surveillance and identification of cases. Full article

(This article belongs to the Topic Discovery and Development of Monkeypox Disease Treatments)

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15 pages, 2712 KiB

Open AccessSystematic Review

Viral Loads in Skin Samples of Patients with Monkeypox Virus Infection: A Systematic Review and Meta-Analysis

by Isha Rani, Prakasini Satapathy, Anmol Goyal, Muhammad Aaqib Shamim, Amit Pal, Rosanna Squitti, Kalyan Goswami, Keerti Bhusan Pradhan, Sarvesh Rustagi, Alaa Hamza Hermis, Joshuan J. Barboza, Alfonso J. Rodriguez-Morales, Ranjit Sah and Bijaya K. Padhi

Viruses 2023, 15(6), 1386; https://doi.org/10.3390/v15061386 - 17 Jun 2023

Cited by 4 | Viewed by 2422

Abstract

Despite monkeypox (mpox) being a public health emergency, there is limited knowledge about the risk of infectivity from skin viral loads during mpox infection. Thus, the aim of this study was to estimate cutaneous viral loads among mpox patients globally. Several databases, including [...] Read more.

Despite monkeypox (mpox) being a public health emergency, there is limited knowledge about the risk of infectivity from skin viral loads during mpox infection. Thus, the aim of this study was to estimate cutaneous viral loads among mpox patients globally. Several databases, including Cochrane, EBSCOHost, EMBASE, ProQuest, PubMed, Scopus, and Web of Science, and preprint servers were searched concerning skin mpox viral loads in confirmed mpox subjects. In this systematic review and meta-analysis, a total of 331 articles were initially screened after the removal of duplicate entries. A total of nine articles were included in the systematic review and meta-analysis for the overall estimation of viral loads (Ct) using a random-effect model. The pooled cutaneous mpox viral load (lower Ct) was 21.71 (95% CI: 20.68–22.75) with a majority of positivity rates being 100%, highlighting a higher infectivity risk from skin lesions. The current results strongly support that skin mpox viral loads may be a dominant source of rapid transmission during current multi-national outbreaks. This important finding can help in constructing useful measures in relevant health policy. Full article

(This article belongs to the Topic Discovery and Development of Monkeypox Disease Treatments)

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14 pages, 2449 KiB

Open AccessReview

VP37 Protein Inhibitors for Mpox Treatment: Highlights on Recent Advances, Patent Literature, and Future Directions

by Shuaibu A. Hudu, Ahmed S. Alshrari, Aiman Al Qtaitat and Mohd Imran

Biomedicines 2023, 11(4), 1106; https://doi.org/10.3390/biomedicines11041106 - 06 Apr 2023

Cited by 4 | Viewed by 1850

Abstract

Monkeypox disease (Mpox) has threatened humankind worldwide since mid-2022. The Mpox virus (MpoxV) is an example of Orthopoxviruses (OPVs), which share similar genomic structures. A few treatments and vaccines are available for Mpox. OPV-specific VP37 protein (VP37P) is a target for developing drugs [...] Read more.

Monkeypox disease (Mpox) has threatened humankind worldwide since mid-2022. The Mpox virus (MpoxV) is an example of Orthopoxviruses (OPVs), which share similar genomic structures. A few treatments and vaccines are available for Mpox. OPV-specific VP37 protein (VP37P) is a target for developing drugs against Mpox and other OPV-induced infections such as smallpox. This review spotlights the existing and prospective VP37P inhibitors (VP37PIs) for Mpox. The non-patent literature was collected from PubMed, and the patent literature was gathered from free patent databases. Very little work has been carried out on developing VP37PIs. One VP37PI (tecovirimat) has already been approved in Europe to treat Mpox, while another drug, NIOCH-14, is under clinical trial. Developing tecovirimat/NIOCH-14-based combination therapies with clinically used drugs demonstrating activity against Mpox or other OPV infections (mitoxantrone, ofloxacin, enrofloxacin, novobiocin, cidofovir, brincidofovir, idoxuridine, trifluridine, vidarabine, fialuridine, adefovir, imatinib, and rifampicin), immunity boosters (vitamin C, zinc, thymoquinone, quercetin, ginseng, etc.), and vaccines may appear a promising strategy to fight against Mpox and other OPV infections. Drug repurposing is also a good approach for identifying clinically useful VP37PIs. The dearth in the discovery process of VP37PIs makes it an interesting area for further research. The development of the tecovirimat/NIOCH-14-based hybrid molecules with certain chemotherapeutic agents looks fruitful and can be explored to obtain new VP37PI. It would be interesting and challenging to develop an ideal VP37PI concerning its specificity, safety, and efficacy. Full article

(This article belongs to the Topic Discovery and Development of Monkeypox Disease Treatments)

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17 pages, 370 KiB

Open AccessReview

Monkeypox Virus in Animals: Current Knowledge of Viral Transmission and Pathogenesis in Wild Animal Reservoirs and Captive Animal Models

by Elizabeth A. Falendysz, Juan G. Lopera, Tonie E. Rocke and Jorge E. Osorio

Viruses 2023, 15(4), 905; https://doi.org/10.3390/v15040905 - 31 Mar 2023

Cited by 9 | Viewed by 3462

Abstract

Mpox, formerly called monkeypox, is now the most serious orthopoxvirus (OPXV) infection in humans. This zoonotic disease has been gradually re-emerging in humans with an increasing frequency of cases found in endemic areas, as well as an escalating frequency and size of epidemics [...] Read more.

Mpox, formerly called monkeypox, is now the most serious orthopoxvirus (OPXV) infection in humans. This zoonotic disease has been gradually re-emerging in humans with an increasing frequency of cases found in endemic areas, as well as an escalating frequency and size of epidemics outside of endemic areas in Africa. Currently, the largest known mpox epidemic is spreading throughout the world, with over 85,650 cases to date, mostly in Europe and North America. These increased endemic cases and epidemics are likely driven primarily by decreasing global immunity to OPXVs, along with other possible causes. The current unprecedented global outbreak of mpox has demonstrated higher numbers of human cases and greater human-to-human transmission than previously documented, necessitating an urgent need to better understand this disease in humans and animals. Monkeypox virus (MPXV) infections in animals, both naturally occurring and experimental, have provided critical information about the routes of transmission; the viral pathogenicity factors; the methods of control, such as vaccination and antivirals; the disease ecology in reservoir host species; and the conservation impacts on wildlife species. This review briefly described the epidemiology and transmission of MPXV between animals and humans and summarizes past studies on the ecology of MPXV in wild animals and experimental studies in captive animal models, with a focus on how animal infections have informed knowledge concerning various aspects of this pathogen. Knowledge gaps were highlighted in areas where future research, both in captive and free-ranging animals, could inform efforts to understand and control this disease in both humans and animals. Full article

(This article belongs to the Topic Discovery and Development of Monkeypox Disease Treatments)

18 pages, 5166 KiB

Open AccessArticle

An Immunoinformatics Approach to Design Novel and Potent Multi-Epitope-Based Vaccine to Target Lumpy Skin Disease

by Muhammad Shahab, A. Khuzaim Alzahrani, Xiuyuan Duan, Muneeba Aslam, Abida, Mohd. Imran, Mehnaz Kamal, Md. Tauquir Alam and Guojun Zheng

Biomedicines 2023, 11(2), 398; https://doi.org/10.3390/biomedicines11020398 - 29 Jan 2023

Cited by 6 | Viewed by 2388

Abstract

The lumpy skin disease (LSD) virus of the Poxviridae family is a serious threat that mostly affects cattle and causes significant economic loss. LSD has the potential to spread widely and its rapidly across borders. Despite the availability of information, there is still [...] Read more.

The lumpy skin disease (LSD) virus of the Poxviridae family is a serious threat that mostly affects cattle and causes significant economic loss. LSD has the potential to spread widely and its rapidly across borders. Despite the availability of information, there is still no competitive vaccine available for LSD. Therefore, the current study was conducted to develop an epitope-based LSD vaccine that is efficient, secure, and biocompatible and stimulates both innate and adaptive immune responses using immunoinformatics techniques. Initially, putative virion core proteins were manipulated; B-cell and T-cell epitopes have been predicted and connected with the help of adjuvants and linkers. Numerous bioinformatics methods, including antigenicity testing, transmembrane topology screening, allergenicity assessment, conservancy analysis, and toxicity evaluation, were employed to find superior epitopes. Based on promising vaccine candidates and immunogenic potential, the vaccine design was selected. Strong interactions between TLR4 and TLR9 and the anticipated vaccine design were revealed by molecular docking. Finally, based on the high docking score, computer simulations were performed in order to assess the stability, efficacy, and compactness of the constructed vaccine. The simulation outcomes showed that the polypeptide vaccine design was remarkably stable, with high expression, stability, immunogenic qualities, and considerable solubility. Additionally, computer-based research shows that the constructed vaccine provides adequate population coverage, making it a promising candidate for use in the design of vaccines against other viruses within the Poxviridae family and potentially other virus families as well. These outcomes suggest that the epitope-based vaccine developed in this study will be a significant candidate against LSD to control and prevent LSDV-related disorders if further investigated experimentally. Full article

(This article belongs to the Topic Discovery and Development of Monkeypox Disease Treatments)

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12 pages, 399 KiB

Open AccessArticle

Monkeypox Cross-Sectional Survey of Knowledge, Attitudes, Practices, and Willingness to Vaccinate among University Students in Pakistan

by Narendar Kumar, Fatima Ahmed, Muhammad Sauban Raza, Pushp Lata Rajpoot, Wajiha Rehman, Shoaib Alam Khatri, Mustapha Mohammed, Shaib Muhammad and Rabbiya Ahmad

Vaccines 2023, 11(1), 97; https://doi.org/10.3390/vaccines11010097 - 31 Dec 2022

Cited by 19 | Viewed by 2848

Abstract

This study aimed to explore knowledge, attitude, perceptions, and willingness regarding vaccination among university students in Pakistan. This cross-sectional study was carried out using an open online self-administered survey via Google Forms. The survey data were collected between the 15 to 30 of [...] Read more.

This study aimed to explore knowledge, attitude, perceptions, and willingness regarding vaccination among university students in Pakistan. This cross-sectional study was carried out using an open online self-administered survey via Google Forms. The survey data were collected between the 15 to 30 of October 2022. A total of 946 respondents participated in the study, of which the majority were female (514, 54.3%). Most students belonged to a medical background, specifically pharmaceutical sciences. Most of the respondents did not know about monkeypox before 2022 (646, 68.3%). Regarding overall knowledge of monkeypox, most of the respondents had average knowledge (726, 76.7%), with very few having good knowledge (60, 6.3%). Regarding overall attitudes towards monkeypox, most of the respondents had neutral attitudes (648, 68.5%). There was a significant association between knowledge of Monkeypox with the type of academic degree (p < 0.001), type of discipline (p < 0.001), and region of respondents (p < 0.001). The willingness to vaccinate among the population was (67.7%). The current study pointed out that the overall knowledge of monkeypox was average in most respondents, with considerable knowledge gaps in most aspects. The overall attitude towards monkeypox was neutral. Further, the knowledge about monkeypox was strongly associated with academic degree, study discipline, and region of respondents. Our findings emphasize the need to raise public awareness by educating students on the monkeypox virus. This will improve adherence to preventative recommendations. Full article

(This article belongs to the Topic Discovery and Development of Monkeypox Disease Treatments)

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