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Viruses
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Diagnostics, Antiviral Therapy and Vaccination against Orthopoxvirus Infections
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Diagnostics, Antiviral Therapy and Vaccination against Orthopoxvirus Infections

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (27 September 2023) | Viewed by 32811

Special Issue Editors

Prof. Dr. Sergei N. Shchelkunov

E-Mail Website
Guest Editor
State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, Koltsovo, Novosibirsk, Russia
Interests: orthopoxviruses; variola virus; monkeypox virus; cowpox virus; vaccinia virus; live attenuated vaccines; clinical trials; viral immunology; diagnostics; virus evolution
Dr. Larisa N. Shishkina

E-Mail Website
Guest Editor
State Research Center of Virology and Biotechnology VECTOR, Rospotrebnadzor, Koltsovo, Novosibirsk, Russia
Interests: antivirals; orthopoxviruses; pre-clinical trials

Special Issue Information

Dear Colleagues,

In the decades since the eradication of smallpox, the human population has almost completely lost herd immunity, not only against smallpox but also against other zoonotic orthopoxviruses. To date, this has led to the fact that outbreaks of human infections caused by monkeypox, cowpox, buffalopox, or vaccinia viruses are increasingly being recorded on different continents, and the risk of widespread epidemics of orthopoxvirus infections is increasing. Therefore, the development of new diagnostic methods, creation of antivirals, and modern vaccines against orthopoxviruses are of particular importance.

This Special Issue will review the latest research findings on the development of express diagnostic methods, the search for effective antivirals, and the creation of modern safe vaccines against orthopoxvirus infections.

Prof. Dr. Sergei N. Shchelkunov
Dr. Larisa N. Shishkina
Guest Editors

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Keywords

  • orthopoxviruses
  • variola (smallpox) virus
  • monkeypox virus
  • cowpox virus
  • buffalopox virus
  • vaccinia virus
  • diagnostics
  • antivirals
  • vaccines
  • viral immunology
  • viral–host interactions
  • animal studies

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Published Papers (7 papers)

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Research

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22 pages, 2274 KiB  
Article
Safety and Pharmacokinetics of the Substance of the Anti-Smallpox Drug NIOCH-14 after Oral Administration to Laboratory Animals
by Larisa N. Shishkina, Oleg Yu. Mazurkov, Nikolai I. Bormotov, Maksim O. Skarnovich, Olga A. Serova, Natalia A. Mazurkova, Maria A. Skarnovich, Alexander A. Chernonosov, Boris A. Selivanov, Alexey Ya. Tikhonov, Svetlana G. Gamaley, Galina G. Shimina, Galina M. Sysoyeva, Oleg S. Taranov, Elena D. Danilenko, Alexander P. Agafonov and Rinat A. Maksyutov
Viruses 2023, 15(1), 205; https://doi.org/10.3390/v15010205 - 11 Jan 2023
Cited by 9 | Viewed by 2549
Abstract
Background: Since most of the modern human population has no anti-smallpox immunity, it is extremely important to develop and implement effective drugs for the treatment of smallpox and other orthopoxvirus infections. The objective of this study is to determine the main characteristics of [...] Read more.
Background: Since most of the modern human population has no anti-smallpox immunity, it is extremely important to develop and implement effective drugs for the treatment of smallpox and other orthopoxvirus infections. The objective of this study is to determine the main characteristics of the chemical substance NIOCH-14 and its safety and bioavailability in the body of laboratory animals. Methods: The safety of NIOCH-14 upon single- or multiple-dose intragastric administration was assessed according to its effect on the main hematological and pathomorphological parameters of laboratory mice and rats. In order to evaluate the pharmacokinetic parameters of NIOCH-14 administered orally, a concentration of ST-246, the active metabolite of NIOCH-14, in mouse blood and organs was determined by tandem mass spectrometry and liquid chromatography. Results: The intragastric administration of NIOCH-14 at a dose of 5 g/kg body weight caused neither death nor signs of intoxication in mice. The intragastric administration of NIOCH-14 to mice and rats at doses of 50 and 150 µg/g body weight either as a single dose or once daily during 30 days did not cause animal death or critical changes in hematological parameters and the microstructure of internal organs. The tissue availability of NIOCH-14 administered orally to the mice at a dose of 50 µg/g body weight, which was calculated according to concentrations of its active metabolite ST-246 for the lungs, liver, kidney, brain, and spleen, was 100, 69.6, 63.3, 26.8 and 20.3%, respectively. The absolute bioavailability of the NIOCH-14 administered orally to mice at a dose of 50 µg/g body weight was 22.8%. Conclusion: Along with the previously determined efficacy against orthopoxviruses, including the smallpox virus, the substance NIOCH-14 was shown to be safe and bioavailable in laboratory animal experiments. Full article
(This article belongs to the Special Issue Diagnostics, Antiviral Therapy and Vaccination against Orthopoxvirus Infections)
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16 pages, 3297 KiB  
Article
Genomic Characterization of the Historical Smallpox Vaccine Strain Wyeth Isolated from a 1971 Seed Vial
by Nádia Vaez G. Cruz, Matheus Nobrega Luques, Terezinha Marta Pereira P. Castiñeiras, Orlando Costa Ferreira Jr, Regina Helena S. Peralta, Luciana J. da Costa and Clarissa R. Damaso
Viruses 2023, 15(1), 83; https://doi.org/10.3390/v15010083 - 28 Dec 2022
Cited by 2 | Viewed by 2733
Abstract
The Wyeth strain of vaccinia virus (VACV) produced by Wyeth Pharmaceuticals was supposedly used to manufacture the old freeze-dried American smallpox vaccine, Dryvax, until its discontinuation in 2008. Although the genomic sequences of numerous Dryvax clones have been reported, data on VACV-Wyeth genomes [...] Read more.
The Wyeth strain of vaccinia virus (VACV) produced by Wyeth Pharmaceuticals was supposedly used to manufacture the old freeze-dried American smallpox vaccine, Dryvax, until its discontinuation in 2008. Although the genomic sequences of numerous Dryvax clones have been reported, data on VACV-Wyeth genomes are still lacking. Genomic analysis of old VACV strains is relevant to understand the evolutionary relationships of smallpox vaccines, particularly with the recent resumption of smallpox vaccination in certain population groups as an attempt to control the worldwide monkeypox outbreak. Here we analyzed the complete genome sequences of three VACV-Wyeth clonal isolates obtained from a single seed vial donated to the Brazilian eradication program in the 1970s. Wyeth clones show >99.3% similarity to each other and >95.3% similarity with Dryvax clones, mapping together in clade I of the vaccinia group. Although the patterns of SNPs and INDELs comparing Dryvax and Wyeth clones are overall uniform, important differences were detected particularly at the ends of the genome. In addition, we detected recombinant events of clone Wyeth A111 and the Dryvax clone Acam2000, suggesting that other regions of the genomes may have similar patchy patterns of recombination. A small-scale serological survey using VACV-Wyeth as antigen in ELISA assays revealed that 63 of the 65 individuals born before the end of smallpox vaccination in Brazil still have anti-VACV IgG antibodies, demonstrating the usefulness of the VACV-Wyeth strain in future extended serological studies of the Brazilian population. Full article
(This article belongs to the Special Issue Diagnostics, Antiviral Therapy and Vaccination against Orthopoxvirus Infections)
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15 pages, 5507 KiB  
Article
Structure-Based Design, Synthesis, and Biological Evaluation of the Cage–Amide Derived Orthopox Virus Replication Inhibitors
by Evgenii S. Mozhaitsev, Evgeniy V. Suslov, Daria A. Rastrepaeva, Olga I. Yarovaya, Sophia S. Borisevich, Edward M. Khamitov, Dmitry S. Kolybalov, Sergey G. Arkhipov, Nikolai I. Bormotov, Larisa N. Shishkina, Olga A. Serova, Roman V. Brunilin, Andrey A. Vernigora, Maxim B. Nawrozkij, Alexander P. Agafonov, Rinat A. Maksyutov, Konstantin P. Volcho and Nariman F. Salakhutdinov
Viruses 2023, 15(1), 29; https://doi.org/10.3390/v15010029 - 21 Dec 2022
Cited by 12 | Viewed by 2863
Abstract
Despite the fact that the variola virus is considered eradicated, the search for new small molecules with activity against orthopoxviruses remains an important task, especially in the context of recent outbreaks of monkeypox. As a result of this work, a number of amides [...] Read more.
Despite the fact that the variola virus is considered eradicated, the search for new small molecules with activity against orthopoxviruses remains an important task, especially in the context of recent outbreaks of monkeypox. As a result of this work, a number of amides of benzoic acids containing an adamantane fragment were obtained. Most of the compounds demonstrated activity against vaccinia virus, with a selectivity index SI = 18,214 for the leader compound 18a. The obtained derivatives also demonstrated activity against murine pox (250 ≤ SI ≤ 6071) and cowpox (125 ≤ SI ≤ 3036). A correlation was obtained between the IC50 meanings and the binding energy to the assumed biological target, the p37 viral protein with R2 = 0.60. Full article
(This article belongs to the Special Issue Diagnostics, Antiviral Therapy and Vaccination against Orthopoxvirus Infections)
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9 pages, 2000 KiB  
Article
Evaluation of Rapid Dot-Immunoassay for Detection Orthopoxviruses Using Laboratory-Grown Viruses and Animal’s Clinical Specimens
by Nikita Ushkalenko, Anna Ersh, Alexander Sergeev, Pavel Filatov and Alexander Poltavchenko
Viruses 2022, 14(11), 2580; https://doi.org/10.3390/v14112580 - 21 Nov 2022
Cited by 4 | Viewed by 1967
Abstract
The aim of the work was an experimental evaluation of the characteristics of the kit for the rapid immunochemical detection of orthopoxviruses (OPV). The kit is based on the method of one-stage dot-immunoassay on flat protein arrays using gold conjugates and a silver [...] Read more.
The aim of the work was an experimental evaluation of the characteristics of the kit for the rapid immunochemical detection of orthopoxviruses (OPV). The kit is based on the method of one-stage dot-immunoassay on flat protein arrays using gold conjugates and a silver developer. Rabbit polyclonal antibodies against the vaccinia virus were used as capture and detection reagents. The sensitivity of detection of OPV and the specificity of the analysis were assessed using culture crude preparations (monkeypox virus, vaccinia virus, rabbitpox virus, cowpox virus, and ectromelia virus), a suspension from a crust from a human vaccination site as well as blood and tissue suspensions of infected rabbits. It has been shown that the assay using the kit makes it possible to detect OPV within 36 min at a temperature of 18–40 °C in unpurified culture samples of the virus and clinical samples in the range of 103–104 PFU/mL. Tests of the kit did not reveal cross-reactivity with uninfected cell cultures and viral pathogens of exanthematous infections (measles, rubella and chicken pox). The kit can be used to detect or exclude the presence of a virus threat in samples and can be useful in various aspects of biosecurity. The simplicity of analysis, the possibility of visual accounting the and interpretation of the results make it possible to use the test in laboratories with a high level of biological protection and in out-of-laboratory conditions. Full article
(This article belongs to the Special Issue Diagnostics, Antiviral Therapy and Vaccination against Orthopoxvirus Infections)
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21 pages, 2397 KiB  
Article
Multi-Epitope Vaccine for Monkeypox Using Pan-Genome and Reverse Vaccinology Approaches
by Rayapadi G. Swetha, Soumya Basu, Sudha Ramaiah and Anand Anbarasu
Viruses 2022, 14(11), 2504; https://doi.org/10.3390/v14112504 - 12 Nov 2022
Cited by 32 | Viewed by 3976
Abstract
Outbreaks of monkeypox virus infections have imposed major health concerns worldwide, with high morbidity threats to children and immunocompromised adults. Although repurposed drugs and vaccines are being used to curb the disease, the evolving traits of the virus, exhibiting considerable genetic dynamicity, challenge [...] Read more.
Outbreaks of monkeypox virus infections have imposed major health concerns worldwide, with high morbidity threats to children and immunocompromised adults. Although repurposed drugs and vaccines are being used to curb the disease, the evolving traits of the virus, exhibiting considerable genetic dynamicity, challenge the limits of a targeted treatment. A pan-genome-based reverse vaccinology approach can provide fast and efficient solutions to resolve persistent inconveniences in experimental vaccine design during an outbreak-exigency. The approach encompassed screening of available monkeypox whole genomes (n = 910) to identify viral targets. From 102 screened viral targets, viral proteins L5L, A28, and L5 were finalized based on their location, solubility, and antigenicity. The potential T-cell and B-cell epitopes were extracted from the proteins using immunoinformatics tools and algorithms. Multiple vaccine constructs were designed by combining the epitopes. Based on immunological properties, chemical stability, and structural quality, a novel multi-epitopic vaccine construct, V4, was finalized. Flexible-docking and coarse-dynamics simulation portrayed that the V4 had high binding affinity towards human HLA-proteins (binding energy < −15.0 kcal/mol) with low conformational fluctuations (<1 Å). Thus, the vaccine construct (V4) may act as an efficient vaccine to induce immunity against monkeypox, which encourages experimental validation and similar approaches against emerging viral infections. Full article
(This article belongs to the Special Issue Diagnostics, Antiviral Therapy and Vaccination against Orthopoxvirus Infections)
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Review

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15 pages, 316 KiB  
Review
Smallpox, Monkeypox and Other Human Orthopoxvirus Infections
by Galina A. Shchelkunova and Sergei N. Shchelkunov
Viruses 2023, 15(1), 103; https://doi.org/10.3390/v15010103 - 29 Dec 2022
Cited by 37 | Viewed by 4598
Abstract
Considering that vaccination against smallpox with live vaccinia virus led to serious adverse effects in some cases, the WHO, after declaration of the global eradication of smallpox in 1980, strongly recommended to discontinue the vaccination in all countries. This led to the loss [...] Read more.
Considering that vaccination against smallpox with live vaccinia virus led to serious adverse effects in some cases, the WHO, after declaration of the global eradication of smallpox in 1980, strongly recommended to discontinue the vaccination in all countries. This led to the loss of immunity against not only smallpox but also other zoonotic orthopoxvirus infections in humans over the past years. An increasing number of human infections with zoonotic orthopoxviruses and, first of all, monkeypox, force us to reconsider a possible re-emergence of smallpox or a similar disease as a result of natural evolution of these viruses. The review contains a brief analysis of the results of studies on genomic organization and evolution of human pathogenic orthopoxviruses, development of modern methods for diagnosis, vaccination, and chemotherapy of smallpox, monkeypox, and other zoonotic human orthopoxvirus infections. Full article
(This article belongs to the Special Issue Diagnostics, Antiviral Therapy and Vaccination against Orthopoxvirus Infections)
24 pages, 2931 KiB  
Review
Monkeypox: A Comprehensive Review
by Harapan Harapan, Youdiil Ophinni, Dewi Megawati, Andri Frediansyah, Sukamto S. Mamada, Mirnawati Salampe, Talha Bin Emran, Wira Winardi, Raisha Fathima, Salin Sirinam, Pichamon Sittikul, Ana M. Stoian, Firzan Nainu and Malik Sallam
Viruses 2022, 14(10), 2155; https://doi.org/10.3390/v14102155 - 29 Sep 2022
Cited by 99 | Viewed by 12902
Abstract
The 2022 multi-country monkeypox outbreak in humans has brought new public health adversity on top of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The disease has spread to 104 countries throughout six continents of the world, with the highest burden in North America [...] Read more.
The 2022 multi-country monkeypox outbreak in humans has brought new public health adversity on top of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The disease has spread to 104 countries throughout six continents of the world, with the highest burden in North America and Europe. The etiologic agent, monkeypox virus (MPXV), has been known since 1959 after isolation from infected monkeys, and virulence among humans has been reported since the 1970s, mainly in endemic countries in West and Central Africa. However, the disease has re-emerged in 2022 at an unprecedented pace, with particular concern on its human-to-human transmissibility and community spread in non-endemic regions. As a mitigation effort, healthcare workers, public health policymakers, and the general public worldwide need to be well-informed on this relatively neglected viral disease. Here, we provide a comprehensive and up-to-date overview of monkeypox, including the following aspects: epidemiology, etiology, pathogenesis, clinical features, diagnosis, and management. In addition, the current review discusses the preventive and control measures, the latest vaccine developments, and the future research areas in this re-emerging viral disease that was declared as a public health emergency of international concern. Full article
(This article belongs to the Special Issue Diagnostics, Antiviral Therapy and Vaccination against Orthopoxvirus Infections)
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