Oral Brincidofovir Therapy for Monkeypox Outbreak: A Focused Review on the Therapeutic Potential, Clinical Studies, Patent Literature, and Prospects

doi:10.3390/biomedicines11020278

Review

. 2023 Jan 19;11(2):278.

doi: 10.3390/biomedicines11020278.

Oral Brincidofovir Therapy for Monkeypox Outbreak: A Focused Review on the Therapeutic Potential, Clinical Studies, Patent Literature, and Prospects

Mohd Imran¹, Mohammed Kanan Alshammari², Mandeep Kumar Arora³, Amit Kumar Dubey³, Sabya Sachi Das³, Mehnaz Kamal⁴, Abdulaziz Saad Abdulrahman Alqahtani⁵, Mohammed Ahmed Yahya Sahloly⁵, Ahmed Hammad Alshammari⁶, Hessah Mohammed Alhomam⁷, Aeshah Mousa Mahzari⁸, Abida¹, Ali A Rabaan^{9

10

11}, Tafadzwa Dzinamarira^{12

13}

Affiliations

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia.
² Department of Clinical Pharmacy, King Fahad Medical City, Riyadh 12211, Saudi Arabia.
³ School of Pharmaceutical and Population Health Informatics, DIT University, Dehradun 248009, Uttarakhand, India.
⁴ Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
⁵ Department of Pharmaceutical Care, Prince Sultan Military Medical City, Riyadh 12233, Saudi Arabia.
⁶ Inventory Control Department, Rafha Maternity and Children Hospital, Rafha 76312, Saudi Arabia.
⁷ College of Clinical Pharmacy, King Faisal University, Al-Hofuf 31982, Saudi Arabia.
⁸ Al-Amal Pharmacy, Jazan 45142, Saudi Arabia.
⁹ Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia.
¹⁰ College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia.
¹¹ Department of Public Health and Nutrition, The University of Haripur, Haripur 22610, Pakistan.
¹² ICAP, Columbia University, Harare P.O. Box 28, Zimbabwe.
¹³ School of Health Systems and Public Health, University of Pretoria, Pretoria 0002, South Africa.

PMID: 36830816
PMCID: PMC9953536
DOI: 10.3390/biomedicines11020278

Review

Oral Brincidofovir Therapy for Monkeypox Outbreak: A Focused Review on the Therapeutic Potential, Clinical Studies, Patent Literature, and Prospects

Mohd Imran et al. Biomedicines. 2023.

. 2023 Jan 19;11(2):278.

doi: 10.3390/biomedicines11020278.

Authors

Affiliations

¹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia.
² Department of Clinical Pharmacy, King Fahad Medical City, Riyadh 12211, Saudi Arabia.
³ School of Pharmaceutical and Population Health Informatics, DIT University, Dehradun 248009, Uttarakhand, India.
⁴ Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
⁵ Department of Pharmaceutical Care, Prince Sultan Military Medical City, Riyadh 12233, Saudi Arabia.
⁶ Inventory Control Department, Rafha Maternity and Children Hospital, Rafha 76312, Saudi Arabia.
⁷ College of Clinical Pharmacy, King Faisal University, Al-Hofuf 31982, Saudi Arabia.
⁸ Al-Amal Pharmacy, Jazan 45142, Saudi Arabia.
⁹ Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia.
¹⁰ College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia.
¹¹ Department of Public Health and Nutrition, The University of Haripur, Haripur 22610, Pakistan.
¹² ICAP, Columbia University, Harare P.O. Box 28, Zimbabwe.
¹³ School of Health Systems and Public Health, University of Pretoria, Pretoria 0002, South Africa.

PMID: 36830816
PMCID: PMC9953536
DOI: 10.3390/biomedicines11020278

Abstract

The monkeypox disease (MPX) outbreak of 2022 has been reported in more than one hundred countries and is becoming a global concern. Unfortunately, only a few treatments, such as tecovirimat (TCV), are available against MPX. Brincidofovir (BCV) is a United States Food and Drug Administration (USFDA)-approved antiviral against smallpox. This article reviews the potential of BCV for treating MPX and other Orthopoxvirus (OPXVs) diseases. The literature for this review was collected from PubMed, authentic websites (USFDA, Chimerix), and freely available patent databases (USPTO, Espacenet, and Patentscope). BCV (a lipophilic derivative of cidofovir) has been discovered and developed by Chimerix Incorporation, USA. Besides smallpox, BCV has also been tested clinically for various viral infections (adenovirus, cytomegalovirus, ebola virus, herpes simplex virus, and double-stranded DNA virus). Many health agencies and reports have recommended using BCV for MPX. However, no health agency has yet approved BCV for MPX. Accordingly, the off-label use of BCV is anticipated for MPX and various viral diseases. The patent literature revealed some important antiviral compositions of BCV. The authors believe there is a huge opportunity to create novel, inventive, and patentable BCV-based antiviral therapies (new combinations with existing antivirals) for OPXVs illnesses (MPX, smallpox, cowpox, camelpox, and vaccinia). It is also advised to conduct drug interaction (food, drug, and disease interaction) and drug resistance investigations on BCV while developing its combinations with other medications. The BCV-based drug repurposing options are also open for further exploration. BCV offers a promising opportunity for biosecurity against OPXV-based bioterrorism attacks and to control the MPX outbreak of 2022.

Keywords: CMX001; Orthopoxvirus; brincidofovir; cidofovir; monkeypox; patent; smallpox.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Chemical structures of BCV and CDV.

**Figure 2**
USFDA regulatory development cycle of BCV.

**Figure 3**
Mechanism of action of BCV.

**Figure 4**
Chemical structures of inactive metabolites of BCV.

See this image and copyright information in PMC

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De la Herrán-Arita AK, González-Galindo C, Inzunza-Leyva GK, Valdez-Flores MA, Norzagaray-Valenzuela CD, Camacho-Zamora A, Batiz-Beltrán JC, Urrea-Ramírez FJ, Romero-Utrilla A, Angulo-Rojo C, Guadrón-Llanos AM, Picos-Cárdenas VJ, Camberos-Barraza J, Rábago-Monzón ÁR, Osuna-Ramos JF. De la Herrán-Arita AK, et al. Microorganisms. 2023 Sep 11;11(9):2287. doi: 10.3390/microorganisms11092287. Microorganisms. 2023. PMID: 37764131 Free PMC article.
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References

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1. Kampf G. Efficacy of biocidal agents and disinfectants against the monkeypox virus and other orthopoxviruses. J. Hosp. Infect. 2022;127:101–110. doi: 10.1016/j.jhin.2022.06.012. - DOI - PMC - PubMed
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[1] MacNeill A.L. Comparative pathology of zoonotic orthopoxviruses. Pathogens. 2022;11:892. doi: 10.3390/pathogens11080892. - DOI - PMC - PubMed

[2] MacNeill A.L. Comparative pathology of zoonotic orthopoxviruses. Pathogens. 2022;11:892. doi: 10.3390/pathogens11080892. - DOI - PMC - PubMed

[3] Kampf G. Efficacy of biocidal agents and disinfectants against the monkeypox virus and other orthopoxviruses. J. Hosp. Infect. 2022;127:101–110. doi: 10.1016/j.jhin.2022.06.012. - DOI - PMC - PubMed

[4] Kampf G. Efficacy of biocidal agents and disinfectants against the monkeypox virus and other orthopoxviruses. J. Hosp. Infect. 2022;127:101–110. doi: 10.1016/j.jhin.2022.06.012. - DOI - PMC - PubMed

[5] Almehmadi M., Allahyani M., Alsaiari A.A., Alshammari M.K., Alharbim A.S., Hussain K.H., Alsubaihi L.I., Kamal M., Alotaibi S.S., Alotaibi A.N., et al. A glance at the development and patent literature of tecovirimat: The first-in-class therapy for emerging monkeypox outbreak. Viruses. 2022;14:1870. doi: 10.3390/v14091870. - DOI - PMC - PubMed

[6] Almehmadi M., Allahyani M., Alsaiari A.A., Alshammari M.K., Alharbim A.S., Hussain K.H., Alsubaihi L.I., Kamal M., Alotaibi S.S., Alotaibi A.N., et al. A glance at the development and patent literature of tecovirimat: The first-in-class therapy for emerging monkeypox outbreak. Viruses. 2022;14:1870. doi: 10.3390/v14091870. - DOI - PMC - PubMed

[7] Multi-Country Outbreak of Monkeypox, External Situation Report #8. [(accessed on 29 October 2022)]. Available online: https://www.who.int/publications/m/item/multi-country-outbreak-of-monkey....

[8] Multi-Country Outbreak of Monkeypox, External Situation Report #8. [(accessed on 29 October 2022)]. Available online: https://www.who.int/publications/m/item/multi-country-outbreak-of-monkey....

[9] Moore M., Zahra F. StatPearls [Internet] StatPearls Publishing; Tampa, FL, USA: 2022. Monkeypox.

[10] Moore M., Zahra F. StatPearls [Internet] StatPearls Publishing; Tampa, FL, USA: 2022. Monkeypox.

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Oral Brincidofovir Therapy for Monkeypox Outbreak: A Focused Review on the Therapeutic Potential, Clinical Studies, Patent Literature, and Prospects

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Oral Brincidofovir Therapy for Monkeypox Outbreak: A Focused Review on the Therapeutic Potential, Clinical Studies, Patent Literature, and Prospects

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