AI Drug Discovery for Pharma and Biotech

Drug discovery

7

drugs

With orphan designations

Overview

Human infection by orthopoxvirus, primarily caused by monkeypox virus (MPXV) and cowpox virus, manifests as a febrile illness with lymphadenopathy and a centrifugal maculopapular rash progressing to pustules. Transmission occurs via zoonotic exposure or close human contact, particularly through skin lesions or respiratory droplets. Post-smallpox eradication, declining population immunity has increased susceptibility, with MPXV emerging as the most clinically significant orthopoxvirus globally. Recent outbreaks highlight expanded human-to-human transmission, particularly in men who have sex with men (MSM), necessitating heightened clinical vigilance [1][6][12][19].

Population

Affects individuals in endemic regions (Central/West Africa), unvaccinated persons under 40, MSM populations (2022–2024 outbreaks), and immunocompromised hosts. Children and young adults experience higher morbidity in resource-limited settings [2][6][12][15].

Burden

  • Clade I (Congo Basin) mortality: ≤10%; clade II (West African): 1–5% [6][12][19].


90,000 global cases (2022–2024), with complications including secondary infections, keratitis, and psychosocial stigma [6][15][19].

  • Economic and healthcare strain in endemic regions due to limited diagnostics and vaccine access [2][5][15].

Therapies

  • Antivirals: Tecovirimat (first-line, FDA-approved for smallpox/mpox) and brincidofovir (reserved for severe cases); cidofovir used off-label [3][13][17].

  • Supportive care: Pain management, hydration, and infection control.

  • Combination therapies: Investigational use of tecovirimat with ACAM2000 vaccine or brincidofovir in high-risk cases [3][8][17].

Categories: rare infectious diseases

Research Papers

1,902 drug discovery papers about Human infection by orthopoxvirus, with 2 first-in-class and 6 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:

1,902 drug discovery papers about Human infection by orthopoxvirus, with 2 first-in-class and 6 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:

2026-06-22 | Human monoclonal antibodies from donors vaccinated with recombinant vaccinia vaccine targeting A35 and B6 effectively inhibit orthopoxvirus spread and infection.

The global Monkeypox (Mpox) outbreak remains ongoing, yet specific therapeutics are still limited. Monkeypox virus (MPXV) proteins A35 and B6 are known to mediate viral cell-to-cell spread within the host. Here, we isolated human monoclonal antibodies (mAbs) targeting MPXV A35 and B6 proteins from the donors received recombinant vaccinia vaccine (rTV). Both A35 mAbs (A35A3, A35A9) and B6 mAbs (B6H1, B6G1) exhibited cross-binding activity against vaccinia virus(VACV) and MPXV, and inhibited cell-to-cell spread of both viruses in vitro. In murine VACV challenge models, A35A3, A35A9, B6H1, and B6G1 conferred significant protection in therapeutic administration. In summary, this study identified four promising candidate mAbs, providing valuable insights for the treatment of orthopoxvirus infections, warranting further validation in MPXV challenge models.

Open article ↗



2026-06-22 | Pan-genome and reverse vaccinology for a multi-epitope vaccine against circulating post-2022 Monkeypox virus strains.

Since the 2022 outbreak, the number of Monkeypox cases worldwide has been increasing at an alarming rate. As of August 2024, approximately 99,000 people have been infected with the virus. The severity of this situation is further highlighted by the World Health Organization's (WHO) classification of the Mpox virus as a Public Health Emergency of International Concern (PHEIC) due to the increased fatality rate of approximately 3.6% in clade I. Targeting the virus's membrane-bound, enveloped, and extracellular proteins, our goal was to computationally develop and assess a broad-spectrum multi-epitope vaccine that elicits humoral and adaptive immune responses against Monkeypox virus (MPXV) infection. During an outbreak, a pan-genome-based reverse vaccinology approach can offer rapid, practical solutions to enduring problems in experimental vaccine design. The method involved screening 16 monkeypox genomes to identify viral targets, from which viral proteins were selected based on their antigenicity, location, and solubility. Immunoinformatics methods and algorithms were used to extract the proteins' putative T-cell and B-cell epitopes, which were combined to form several vaccine constructions. The tertiary structure of the chimeric vaccine construct's interaction with Toll-like receptor 4 (TLR4) was thoroughly assessed using the advanced techniques of molecular docking and molecular dynamics simulation. A pan-genomic analysis identified 80 core genes, which were then screened for proteins suitable for epitope-based vaccine design. From four of these selected proteins, T-cell and B-cell epitopes were extracted to create four distinct vaccine constructs. Appropriate adjuvants and linkers were incorporated into each construct to enhance its potential efficacy. Stability and immunogenicity analyses of each vaccine design yielded promising results. These findings suggest that the vaccine constructs could be effective in preventing monkeypox, warranting further experimental validation and supporting the application of similar strategies to combat other viral illnesses.

Open article ↗



2026-06-19 | Epidemiology and characteristics of cases with monkeypox virus clade I in the WHO European Region, 2024 to 2025.

BACKGROUNDA public health emergency of international concern (PHEIC) was declared in August 2024 following a sharp increase in mpox cases linked to the emergence of monkeypox virus (MPXV) clade Ib.AIMWe aimed to characterise imported and locally acquired mpox clade I cases reported in the WHO European Region (WHO/Europe) since August 2024 and assess transmission patterns and response measures.METHODSWe collected data on MPXV clade I infections reported by countries in WHO/Europe through the International Health Regulations. We contacted reporting countries to collect age, sex, travel history, most likely route of transmission, clinical course, contacts and type of exposure, and implemented control and prevention measures.RESULTSBetween 14 August 2024 and 23 November 2025, 82 cases of MPXV clade I infection were reported; 45 were imported and 37 were infected in reporting countries. Seventy-nine were typed as clade Ib and two as clade Ia. Most imported cases reported heterosexual (n = 26) or close physical contact (n = 5) as possible exposure. Secondary transmission occurred in six households. One healthcare worker was infected. Since October 2025, further 17 autochthonous male cases were most likely infected through sex with other men.CONCLUSIONImported cases of MPXV clade I infection were associated with limited household transmission. The increase in autochthonous infections among men with recent sexual contact with other men suggests undetected spread in Europe, that may become sustained. Continued surveillance, case and contact investigation are needed to understand MPXV clade I epidemiology and drivers of MPXV clade I transmission in Europe.

Open article ↗



2026-06-22 | Human monoclonal antibodies from donors vaccinated with recombinant vaccinia vaccine targeting A35 and B6 effectively inhibit orthopoxvirus spread and infection.

The global Monkeypox (Mpox) outbreak remains ongoing, yet specific therapeutics are still limited. Monkeypox virus (MPXV) proteins A35 and B6 are known to mediate viral cell-to-cell spread within the host. Here, we isolated human monoclonal antibodies (mAbs) targeting MPXV A35 and B6 proteins from the donors received recombinant vaccinia vaccine (rTV). Both A35 mAbs (A35A3, A35A9) and B6 mAbs (B6H1, B6G1) exhibited cross-binding activity against vaccinia virus(VACV) and MPXV, and inhibited cell-to-cell spread of both viruses in vitro. In murine VACV challenge models, A35A3, A35A9, B6H1, and B6G1 conferred significant protection in therapeutic administration. In summary, this study identified four promising candidate mAbs, providing valuable insights for the treatment of orthopoxvirus infections, warranting further validation in MPXV challenge models.

Open article ↗



2026-06-22 | Pan-genome and reverse vaccinology for a multi-epitope vaccine against circulating post-2022 Monkeypox virus strains.

Since the 2022 outbreak, the number of Monkeypox cases worldwide has been increasing at an alarming rate. As of August 2024, approximately 99,000 people have been infected with the virus. The severity of this situation is further highlighted by the World Health Organization's (WHO) classification of the Mpox virus as a Public Health Emergency of International Concern (PHEIC) due to the increased fatality rate of approximately 3.6% in clade I. Targeting the virus's membrane-bound, enveloped, and extracellular proteins, our goal was to computationally develop and assess a broad-spectrum multi-epitope vaccine that elicits humoral and adaptive immune responses against Monkeypox virus (MPXV) infection. During an outbreak, a pan-genome-based reverse vaccinology approach can offer rapid, practical solutions to enduring problems in experimental vaccine design. The method involved screening 16 monkeypox genomes to identify viral targets, from which viral proteins were selected based on their antigenicity, location, and solubility. Immunoinformatics methods and algorithms were used to extract the proteins' putative T-cell and B-cell epitopes, which were combined to form several vaccine constructions. The tertiary structure of the chimeric vaccine construct's interaction with Toll-like receptor 4 (TLR4) was thoroughly assessed using the advanced techniques of molecular docking and molecular dynamics simulation. A pan-genomic analysis identified 80 core genes, which were then screened for proteins suitable for epitope-based vaccine design. From four of these selected proteins, T-cell and B-cell epitopes were extracted to create four distinct vaccine constructs. Appropriate adjuvants and linkers were incorporated into each construct to enhance its potential efficacy. Stability and immunogenicity analyses of each vaccine design yielded promising results. These findings suggest that the vaccine constructs could be effective in preventing monkeypox, warranting further experimental validation and supporting the application of similar strategies to combat other viral illnesses.

Open article ↗



2026-06-19 | Epidemiology and characteristics of cases with monkeypox virus clade I in the WHO European Region, 2024 to 2025.

BACKGROUNDA public health emergency of international concern (PHEIC) was declared in August 2024 following a sharp increase in mpox cases linked to the emergence of monkeypox virus (MPXV) clade Ib.AIMWe aimed to characterise imported and locally acquired mpox clade I cases reported in the WHO European Region (WHO/Europe) since August 2024 and assess transmission patterns and response measures.METHODSWe collected data on MPXV clade I infections reported by countries in WHO/Europe through the International Health Regulations. We contacted reporting countries to collect age, sex, travel history, most likely route of transmission, clinical course, contacts and type of exposure, and implemented control and prevention measures.RESULTSBetween 14 August 2024 and 23 November 2025, 82 cases of MPXV clade I infection were reported; 45 were imported and 37 were infected in reporting countries. Seventy-nine were typed as clade Ib and two as clade Ia. Most imported cases reported heterosexual (n = 26) or close physical contact (n = 5) as possible exposure. Secondary transmission occurred in six households. One healthcare worker was infected. Since October 2025, further 17 autochthonous male cases were most likely infected through sex with other men.CONCLUSIONImported cases of MPXV clade I infection were associated with limited household transmission. The increase in autochthonous infections among men with recent sexual contact with other men suggests undetected spread in Europe, that may become sustained. Continued surveillance, case and contact investigation are needed to understand MPXV clade I epidemiology and drivers of MPXV clade I transmission in Europe.

Open article ↗



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Drug Discovery Landscape

7 orphan drug designations for Human infection by orthopoxvirus, including 2 approved therapies.

7 orphan drug designations for Human infection by orthopoxvirus, including 2 approved therapies.

Drug

Therapy type

Regulator

Orphan designation

Approval

Sponsor

brincidofovir [Tembexa]

small molecules

FDA

2018-06-05

2021-06-04

Emergent BioDefense Operations Lansing LLC

Brincidofovir

small molecules

EMA

2016-11-18

Emergent Operations Ireland Limited

Tecovirimat

small molecules

EMA

2010-10-01

SIGA Pharmaceuticals (Europe) Limited

tecovirimat

small molecules

FDA

2010-09-29

SIGA Technologies, Inc.

tecovirimat [TPOXX]

small molecules

FDA

2006-12-27

2018-07-13

SIGA Technologies, Inc.

tecovirimat

small molecules

FDA

2006-12-18

SIGA Technologies, Inc.

polyinosinic-polycytidilic acid (Poly-ICLC)

oligonucleotides

FDA

2002-11-19

Oncovir

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At Explority, we build first-of-its-kind AI to bring clarity to the earliest and riskiest stages of pharmaceutical research by forecasting which therapies are most likely to succeed. Explority AI web and mobile applications are properties of the Explority AI Inc., a company registered in the United States (File No. 10320493).
For all questions: support@explority.ai

Copyright © 2026 Explority AI Inc.

Explority AI logo

228 Park Ave S,
New York, USA.

At Explority, we build first-of-its-kind AI to bring clarity to the earliest and riskiest stages of pharmaceutical research by forecasting which therapies are most likely to succeed. Explority AI web and mobile applications are properties of the Explority AI Inc., a company registered in the United States (File No. 10320493).
For all questions: support@explority.ai

Copyright © 2026 Explority AI Inc.

Explority AI logo

228 Park Ave S,
New York, USA.

At Explority, we build first-of-its-kind AI to bring clarity to the earliest and riskiest stages of pharmaceutical research by forecasting which therapies are most likely to succeed. Explority AI web and mobile applications are properties of the Explority AI Inc., a company registered in the United States (File No. 10320493).
For all questions: support@explority.ai

Copyright © 2026 Explority AI Inc.