Pharmacological treatment and vaccines in monkeypox virus: a narrative review and bibliometric analysis

Mpox (earlier known as monkeypox) virus infection is a recognized public health emergency. There has been little research on the treatment options. This article reviews the specific drugs used to treat mpox virus infection and the vaccines used here. Instead of focusing on the mechanistic basis, this review narrates the practical, real-life experiences of individual patients of mpox virus disease being administered these medicines. We conducted a bibliometric analysis on the treatment of the mpox virus using data from several databases like PubMed, Scopus, and Embase. The research on this topic has grown tremendously recently but it is highly concentrated in a few countries. Cidofovir is the most studied drug. This is because it is indicated and also used off-label for several conditions. The drugs used for mpox virus infection include tecovirimat, cidofovir, brincidofovir, vaccinia immune globulin, and trifluridine. Tecovirimat is used most frequently. It is a promising option in progressive mpox disease in terms of both efficacy and safety. Brincidofovir has been associated with treatment discontinuation due to elevated hepatic enzymes. Cidofovir is also not the preferred drug, often used because of the unavailability of tecovirimat. Trifluridine is used topically as an add-on agent along with tecovirimat for ocular manifestations of mpox virus disease. No study reports individual patient data for vaccinia immune globulin. Though no vaccine is currently approved for mpox virus infection, ACAM 2000 and JYNNEOS are the vaccines being mainly considered. ACAM 2000 is capable of replicating and may cause severe adverse reactions. It is used when JYNNEOS is contraindicated. Several drugs and vaccines are under development and have been discussed alongside pragmatic aspects of mpox virus treatment and prevention. Further studies can provide more insight into the safety and efficacy of Tecovirimat in actively progressing mpox virus disease.

[1]  V. S. Mattaparthi,et al.  Identification of FDA-approved drugs with triple targeting mode of action for the treatment of monkeypox: a high throughput virtual screening study , 2023, Molecular diversity.

[2]  Jielu Yan,et al.  Mpox multi-antigen mRNA vaccine candidates by a simplified manufacturing strategy afford efficient protection against lethal orthopoxvirus challenge , 2023, Emerging microbes & infections.

[3]  Fatma Labieb,et al.  Monkeypox pandemic containment: does the ACAM2000 vaccine play a role in the current outbreaks? , 2023, Expert review of vaccines.

[4]  M. Imran,et al.  VP37 Protein Inhibitors for Mpox Treatment: Highlights on Recent Advances, Patent Literature, and Future Directions , 2023, Biomedicines.

[5]  A. Masud,et al.  Effect of prior immunisation with smallpox vaccine for protection against human Mpox: A systematic review , 2023, Reviews in medical virology.

[6]  C. Kundu,et al.  Advances in nanomedicine for the treatment of infectious diseases caused by viruses. , 2023, Biomaterials science.

[7]  Iqra Naeem,et al.  In-silico targeting TMPK from monkey pox virus: Molecular docking analysis, density functional theory studies and molecular dynamic simulation analysis , 2023, Journal of biomolecular structure & dynamics.

[8]  Parth Sarthi Sen Gupta,et al.  Identification and Investigation of a Cryptic Binding Pocket of the P37 Envelope Protein of Monkeypox Virus by Molecular Dynamics Simulations. , 2023, The journal of physical chemistry letters.

[9]  Rakesh Kaundal,et al.  Deciphering the complete human-monkeypox virus interactome: Identifying immune responses and potential drug targets , 2023, Frontiers in Immunology.

[10]  J. Reina,et al.  Vaccines against monkeypox , 2023, Medicina clinica.

[11]  Qi Chen,et al.  Rational development of multicomponent mRNA vaccine candidates against mpox , 2023, Emerging microbes & infections.

[12]  Rohit Kumar Sharma,et al.  Anti-viral drug discovery against monkeypox and smallpox infection by natural curcumin derivatives: A Computational drug design approach , 2023, Frontiers in Cellular and Infection Microbiology.

[13]  D. Kelvin,et al.  Drug repurposing for Mpox: Discovery of small molecules as potential inhibitors against DNA‐dependent RNA polymerase using molecular modeling approach , 2023, Journal of cellular biochemistry.

[14]  Xing Sun,et al.  Evidence synthesis of Chinese medicine for monkeypox: Suggestions from other contagious pox-like viral diseases , 2023, Frontiers in Pharmacology.

[15]  P. Pan,et al.  Development of multi-epitope vaccines against the monkeypox virus based on envelope proteins using immunoinformatics approaches , 2023, Frontiers in Immunology.

[16]  Caroline A. Schrodt,et al.  Interim Clinical Treatment Considerations for Severe Manifestations of Mpox — United States, February 2023 , 2023, MMWR. Morbidity and mortality weekly report.

[17]  M. Arasu,et al.  Molecular docking of monkeypox (mpox) virus proteinase with FDA approved lead molecules , 2023, Journal of infection and public health.

[18]  Y. Waheed,et al.  Structure-based design of promising natural products to inhibit thymidylate kinase from Monkeypox virus and validation using free energy calculations , 2023, Comput. Biol. Medicine.

[19]  B. Padhi,et al.  Ophthalmic Manifestations of the Monkeypox Virus: A Systematic Review and Meta-Analysis , 2023, Pathogens.

[20]  B. Padhi,et al.  Oral manifestation of the monkeypox virus: a systematic review and meta-analysis , 2023, EClinicalMedicine.

[21]  S. Galvin,et al.  Tecovirimat Use in Ambulatory and Hospitalized Patients with Monkeypox Virus Infection. , 2022, Sexually transmitted diseases.

[22]  A. Al-Harrasi,et al.  Designing multi-epitope monkeypox virus-specific vaccine using immunoinformatics approach , 2022, Journal of infection and public health.

[23]  J. Chow,et al.  Treatment of ocular-involving monkeypox virus with topical trifluridine and oral tecovirimat in the 2022 monkeypox virus outbreak , 2022, American journal of ophthalmology case reports.

[24]  Abhishek S. Rao,et al.  Translational vaccinomics and structural filtration algorithm to device multiepitope vaccine for catastrophic monkeypox virus , 2022, Comput. Biol. Medicine.

[25]  J. Cole,et al.  Monkeypox encephalitis with transverse myelitis in a female patient , 2022, The Lancet. Infectious diseases.

[26]  V. Chattu,et al.  Potentially Asymptomatic Infection of Monkeypox Virus: A Systematic Review and Meta-Analysis , 2022, Vaccines.

[27]  Vijay Kumar Chattu,et al.  The use of antivirals in the treatment of human monkeypox outbreaks: a systematic review , 2022, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[28]  Guangdi Li,et al.  Therapeutic strategies for human poxvirus infections: Monkeypox (mpox), smallpox, molluscipox, and orf , 2022, Travel medicine and infectious disease.

[29]  M. Okpeku,et al.  Global Research Trends on Monkeypox Virus: A Bibliometric and Visualized Study , 2022, Tropical medicine and infectious disease.

[30]  Heidi M. Torres.  Current Options in the Diagnosis and Treatment of Monkeypox , 2022, Current Fungal Infection Reports.

[31]  J. Zucker,et al.  New Perspectives on Antimicrobial Agents: Tecovirimat for Treatment of Human Monkeypox Virus , 2022, Antimicrobial agents and chemotherapy.

[32]  A. Rabaan,et al.  Monkeypox outbreak 2022: What we know so far and its potential drug targets and management strategies , 2022, Journal of medical virology.

[33]  C. Fabrizio,et al.  Cidofovir for treating complicated monkeypox in a man with acquired immune deficiency syndrome , 2022, Infection.

[34]  I. Udell,et al.  Ocular Pox Lesions in a Male Patient With Monkeypox Treated With Tecovirimat. , 2022, JAMA ophthalmology.

[35]  Wei Wang,et al.  Monkeypox: epidemiology, pathogenesis, treatment and prevention , 2022, Signal Transduction and Targeted Therapy.

[36]  E. Nicastri,et al.  Clinical experience with use of oral Tecovirimat or Intravenous Cidofovir for the treatment of Monkeypox in an Italian reference hospital , 2022, The Journal of infection.

[37]  J. Gonzales-Zamora,et al.  Severe monkeypox with superimposed bacterial infection in an immunocompetent patient: A case report , 2022, IDCases.

[38]  F. Davies,et al.  The clinical presentation of monkeypox: a retrospective case-control study of patients with possible or probable monkeypox in a West London cohort , 2022, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[39]  A. Rodríguez-Morales,et al.  Antiviral Treatment against Monkeypox: A Scoping Review , 2022, Tropical medicine and infectious disease.

[40]  M. Díaz-Menéndez,et al.  Human monkeypox outbreak: Epidemiological data and therapeutic potential of topical cidofovir in a prospective cohort study , 2022, Journal of the American Academy of Dermatology.

[41]  A. Casadevall,et al.  The Potential Role of Passive Antibody-Based Therapies as Treatments for Monkeypox , 2022, mBio.

[42]  R. Oliva,et al.  Immunoinformatics-Aided Design of a Peptide Based Multiepitope Vaccine Targeting Glycoproteins and Membrane Proteins against Monkeypox Virus , 2022, Viruses.

[43]  M. Bhattacharya,et al.  Monkeypox virus vaccine evolution and global preparedness for vaccination , 2022, International immunopharmacology.

[44]  Gail L. Thompson,et al.  Ocular Monkeypox — United States, July–September 2022 , 2022, MMWR. Morbidity and mortality weekly report.

[45]  F. Almajhdi,et al.  Contriving multi-epitope vaccine ensemble for monkeypox disease using an immunoinformatics approach , 2022, Frontiers in Immunology.

[46]  C. Pasquier,et al.  A severe monkeypox infection in a patient with an advanced HIV infection treated with tecovirimat: clinical and virological outcome , 2022, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[47]  N. Maffulli,et al.  Monkeypox: An Emerging Global Public Health Emergency , 2022, Life.

[48]  T. Hedberg,et al.  Human Monkeypox Virus Infection in the Immediate Period After Receiving Modified Vaccinia Ankara Vaccine. , 2022, JAMA.

[49]  Amanda L. Piquet,et al.  Two Cases of Monkeypox-Associated Encephalomyelitis — Colorado and the District of Columbia, July–August 2022 , 2022, MMWR. Morbidity and mortality weekly report.

[50]  K. O'Laughlin,et al.  Clinical Use of Tecovirimat (Tpoxx) for Treatment of Monkeypox Under an Investigational New Drug Protocol — United States, May–August 2022 , 2022, MMWR. Morbidity and mortality weekly report.

[51]  R. Kirsner,et al.  Human monkeypox virus infection in an immunocompromised man: trial with tecovirimat , 2022, The Lancet.

[52]  A. Elfiky,et al.  Repurposing antiviral drugs against the human monkeypox virus DNA-dependent RNA polymerase; in silico perspective , 2022, The Journal of infection.

[53]  Hisham N. Altayb.  Fludarabine, a Potential DNA-Dependent RNA Polymerase Inhibitor, as a Prospective Drug against Monkeypox Virus: A Computational Approach , 2022, Pharmaceuticals.

[54]  P. Horby,et al.  Monkeypox treatment with tecovirimat in the Central African Republic under an Expanded Access Programme , 2022, medRxiv.

[55]  Mohd Imran,et al.  A Glance at the Development and Patent Literature of Tecovirimat: The First-in-Class Therapy for Emerging Monkeypox Outbreak , 2022, Viruses.

[56]  Chunhua Li,et al.  Multi-epitope chimeric vaccine design against emerging Monkeypox virus via reverse vaccinology techniques- a bioinformatics and immunoinformatics approach , 2022, Frontiers in Immunology.

[57]  Stuart H. Cohen,et al.  Compassionate Use of Tecovirimat for the Treatment of Monkeypox Infection. , 2022, JAMA.

[58]  T. Palmore,et al.  Monkeypox Virus–Associated Severe Proctitis Treated With Oral Tecovirimat: A Report of Two Cases , 2022, Annals of Internal Medicine.

[59]  V. Selvaraj,et al.  Inpatient Management of Monkeypox , 2022, Brown Journal of Hospital Medicine.

[60]  J. Brooks,et al.  Tecovirimat and the Treatment of Monkeypox - Past, Present, and Future Considerations. , 2022, The New England journal of medicine.

[61]  Kwang Su Kim,et al.  Potential anti-monkeypox virus activity of atovaquone, mefloquine, and molnupiravir, and their potential use as treatments , 2022, bioRxiv.

[62]  Y. Yazdanpanah,et al.  Clinical characteristics of ambulatory and hospitalized patients with monkeypox virus infection: an observational cohort study , 2022, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[63]  S. Nozza,et al.  Unilateral Blepharoconjunctivitis due to Monkeypox Virus Infection , 2022, Ophthalmology.

[64]  M. Aepfelbacher,et al.  Clinical characteristics and comparison of longitudinal qPCR results from different specimen types in a cohort of ambulatory and hospitalized patients infected with monkeypox virus. , 2022, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[65]  S. Peters,et al.  Oral Manifestations of Monkeypox: A Report of 2 Cases , 2022, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons.

[66]  A. Giacomelli,et al.  Hospitalisation for monkeypox in Milan, Italy , 2022, Travel medicine and infectious disease.

[67]  Joseph Sassine,et al.  Antivirals With Activity Against Mpox: A Clinically Oriented Review , 2022, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[68]  Jennifer A. Johnson,et al.  Tecovirimat for the Treatment of Human Monkeypox: An Initial Series From Massachusetts, United States , 2022, Open forum infectious diseases.

[69]  Kunal M. Ajmera,et al.  Monkeypox – An emerging pandemic , 2022, IDCases.

[70]  A. Castagna,et al.  Monkeypox infection among men who have sex with men: PCR testing on seminal fluids , 2022, The Journal of infection.

[71]  J. Kaler,et al.  Monkeypox: A Comprehensive Review of Transmission, Pathogenesis, and Manifestation , 2022, Cureus.

[72]  Jiyuan Zhang,et al.  Monkeypox outbreak: A novel threat after COVID-19? , 2022, Military Medical Research.

[73]  G. Lippi,et al.  Prevention and Treatment of Monkeypox , 2022, Drugs.

[74]  Kunming Cheng,et al.  Bibliometric analysis of global research trends on monkeypox: Are we ready to face this challenge? , 2022, Journal of medical virology.

[75]  Jennifer L. Small,et al.  Clinical features and management of human monkeypox: a retrospective observational study in the UK , 2022, The Lancet. Infectious diseases.

[76]  Caroline A. Schrodt,et al.  Monkeypox in a Traveler Returning from Nigeria — Dallas, Texas, July 2021 , 2022, MMWR. Morbidity and mortality weekly report.

[77]  Coulter Small,et al.  Monkeypox infection and resolution after treatment with tecovirimat in two patients with HIV disease , 2022, Therapeutic advances in infectious disease.

[78]  I. Malami,et al.  Traditional medicinal plants used for treating emerging and re-emerging viral diseases in northern Nigeria , 2021, European journal of integrative medicine.

[79]  C. Shea,et al.  Topical cidofovir for benign human papillomavirus–associated skin lesions , 2021, Antiviral therapy.

[80]  M. Moossavi,et al.  Treatment of acyclovir-resistant herpes simplex virus with intralesional cidofovir , 2021, JAAD case reports.

[81]  A. Ferrer,et al.  Intravesical cidofovir, use in BK polyomavirus-associated haemorrhagic cystitis after haematopoietic stem cell transplantation: off-label. , 2021, Nefrologia.

[82]  A. Chernonosov,et al.  Estimation of Absolute Bioavailability of the Chemical Substance of the Anti-Smallpox Preparation NIOCH-14 in Mice , 2020, Bulletin of Experimental Biology and Medicine.

[83]  A. Klein,et al.  Trends in recurrent respiratory papillomatosis treatment. , 2020, Acta otorrinolaringologica espanola.

[84]  G. Boivin,et al.  Clinical development of letermovir and maribavir: Overview of human cytomegalovirus drug resistance , 2019, Antiviral research.

[85]  R. Bambara,et al.  Cidofovir Diphosphate Inhibits Adenovirus 5 DNA Polymerase via both Nonobligate Chain Termination and Direct Inhibition, and Polymerase Mutations Confer Cidofovir Resistance on Intact Virus , 2018, Antimicrobial Agents and Chemotherapy.

[86]  S. Shivaprasad.  Cidofovir , 2018, Reactions Weekly.

[87]  Sheridan M. Hoy.  Tecovirimat: First Global Approval , 2018, Drugs.

[88]  M. Gunzburg,et al.  Structural basis for the inhibition of poxvirus assembly by the antibiotic rifampicin , 2018, Proceedings of the National Academy of Sciences.

[89]  FDA approves the first drug with an indication for treatment of smallpox , 2018, Case Medical Research.

[90]  M. Reynolds,et al.  Improving the Care and Treatment of Monkeypox Patients in Low-Resource Settings: Applying Evidence from Contemporary Biomedical and Smallpox Biodefense Research , 2017, Viruses.

[91]  T. Walsh,et al.  Drug development challenges and strategies to address emerging and resistant fungal pathogens , 2017, Expert review of anti-infective therapy.

[92]  A. Agafonov,et al.  The Possibility of Using the ICR Mouse as an Animal Model to Assess Antimonkeypox Drug Efficacy. , 2016, Transboundary and emerging diseases.

[93]  A. A. Sergeev,et al.  New effective chemically synthesized anti-smallpox compound NIOCH-14. , 2016, The Journal of general virology.

[94]  R. Kennedy,et al.  Defending against smallpox: a focus on vaccines , 2016, Expert review of vaccines.

[95]  A. Agafonov,et al.  Using ICR and SCID mice as animal models for smallpox to assess antiviral drug efficacy. , 2015, The Journal of general virology.

[96]  J. J. van den Oord,et al.  KAY-2-41, a Novel Nucleoside Analogue Inhibitor of Orthopoxviruses In Vitro and In Vivo , 2013, Antimicrobial Agents and Chemotherapy.

[97]  E. Kern,et al.  Orthopoxvirus targets for the development of new antiviral agents. , 2012, Antiviral research.

[98]  R. Razonable.  Antiviral Drugs for Viruses Other Than Human Immunodeficiency Virus , 2011, Mayo Clinic Proceedings.

[99]  R. Jordan,et al.  Development of the small-molecule antiviral ST-246 as a smallpox therapeutic. , 2011, Future virology.

[100]  G. Pauli,et al.  Orthopox Viruses: Infections in Humans , 2010, Transfusion Medicine and Hemotherapy.

[101]  E. Zumbrun,et al.  ACAM2000™: The new smallpox vaccine for United States Strategic National Stockpile , 2010, Drug design, development and therapy.

[102]  Derek R. Smith,et al.  Bibliometrics, dermatology and contact dermatitis , 2008, Contact dermatitis.

[103]  E. De Clercq,et al.  Activity of the Anti-Orthopoxvirus Compound ST-246 against Vaccinia, Cowpox and Camelpox Viruses in Cell Monolayers and Organotypic Raft Cultures , 2007, Antiviral therapy.

[104]  D. Smee,et al.  Efficacy of N-methanocarbathymidine in treating mice infected intranasally with the IHD and WR strains of vaccinia virus. , 2007, Antiviral research.

[105]  A. Kazory,et al.  Simultaneous development of Fanconi syndrome and acute renal failure associated with cidofovir. , 2007, The Journal of antimicrobial chemotherapy.

[106]  S. Bavari,et al.  Reemergence of monkeypox: prevalence, diagnostics, and countermeasures. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[107]  P. Wutzler,et al.  In vitro activity of cycloSal-nucleoside monophosphates and polyhydroxycarboxylates against orthopoxviruses. , 2005, Antiviral research.

[108]  E. Kern,et al.  Orthopoxvirus targets for the development of antiviral therapies. , 2005, Current drug targets. Infectious disorders.

[109]  R. Hopkins,et al.  Clinical efficacy of intramuscular vaccinia immune globulin: a literature review. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[110]  E. De Clercq.  Clinical Potential of the Acyclic Nucleoside Phosphonates Cidofovir, Adefovir, and Tenofovir in Treatment of DNA Virus and Retrovirus Infections , 2003, Clinical Microbiology Reviews.

[111]  C. A. Rodriguez,et al.  Pharmacokinetics and Renal Effects of Cidofovir with a Reduced Dose of Probenecid in HIV‐Infected Patients with Cytomegalovirus Retinitis , 2003, Journal of clinical pharmacology.

[112]  Kevin B. Wynne,et al.  Anterior uveitis associated with intravenous cidofovir use in patients with cytomegalovirus retinitis , 1999, The British journal of ophthalmology.

[113]  K. Cundy.  Clinical Pharmacokinetics of the Antiviral Nucleotide Analogues Cidofovir and Adefovir , 1999, Clinical pharmacokinetics.

[114]  A. Tseng,et al.  Iritis Associated with Intravenous Cidofovir , 1999, The Annals of pharmacotherapy.

[115]  J. Cherrington,et al.  In vitro antiviral susceptibilities of isolates from cytomegalovirus retinitis patients receiving first- or second-line cidofovir therapy: relationship to clinical outcome. , 1998, The Journal of infectious diseases.

[116]  P. Fan-Havard,et al.  Cidofovir in the Treatment of Cytomegaloviral Disease , 1998, The Annals of pharmacotherapy.

[117]  R. N. Brogden,et al.  Trifluridine: A Review of its Antiviral Activity and Therapeutic Use in the Topical Treatment of Viral Eye Infections , 1982, Drugs.

[118]  Smallpox eradication. WHO Advisory Committee on variola virus research. , 2000, Releve epidemiologique hebdomadaire.