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

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.

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

“…Vaccinia virus is the prototype of OPVs and has an established replication cycle. Accordingly, numerous Vaccinia virus-based molecular drug targets for developing anti-OPV drugs have been reported in the literature ( Table 3 ) [ 3 , 10 , 14 , 19 , 20 ].…”

“…The updated literature (patent and non-patent) for this manuscript was collected on 17 January 2023, from PubMed and different free patent databases (Espacenet, Patentscope, and USPTO) utilizing various keywords (VP37, p37, F13L, Mpox, smallpox, Orthopoxvirus, tecovirimat, TPOXX, ST-246, SIGA-246, NIOCH-14, and IMCBH) and their combinations [ 3 , 14 ]. The identical results were removed, and the literature relevant to the subject matter was selected for writing this article.…”

“…For a virus to strive and cause infection, it must effectively recognize, penetrate, uncoat, and synthesize all the required proteins needed to form a matured virus. The replication cycle of an OPV is provided in Figure 2 [ 3 , 14 , 19 , 20 , 22 ].…”

Anti‐Monkeypox Infection Approaches: From Prevention to Therapeutic Lines

“…As a result, renal function (serum creatinine and urine protein) must be monitored 48 h before each dose of cidofovir, and dose adjustments must be made if renal function changes 20,58‐60 . In general, brincidofovir, a prodrug of cidofovir, has a better safety profile than cidofovir, with no reports of serious renal toxicity or other adverse events in the treatment of CMV and Mpox infection when compared to cidofovir 61,62 …”

“…20,[58][59][60] In general, brincidofovir, a prodrug of cidofovir, has a better safety profile than cidofovir, with no reports of serious renal toxicity or other adverse events in the treatment of CMV and Mpox infection when compared to cidofovir. 61,62…”