Efficacy of three key antiviral drugs used to treat orthopoxvirus infections: a systematic review

Abstract

Background: In a global political climate increasingly concerned about terrorism, bioterrorism agents such as smallpox would undoubtedly be catastrophic. Since WHO announced the eradication of smallpox in 1980, consequently discontinuing the worldwide vaccination campaign, today's population is either immunologically naïve or has waning levels of protection. Further, up to 25% of today's population are contraindicated for smallpox vaccination due to various immunodeficiency conditions. The aim of this study was to evaluate the efficacy of the anti-DNA antivirals cidofovir (CDV), brincidofovir (BCV) and tecovirimat against smallpox and other orthopoxviruses. As of July 2018, FDA approved tecovirimat as the first treatment for smallpox. Methods: A systematic review was conducted to identify relevant literature describing the efficacy and safety of CDV, BCV and tecovirimat including in vitro and in vivo animal studies, human safety trials and human case reports of orthopoxvirus infection. Results: 158 studies met the inclusion criteria. In vitro and in vivo animal studies have found that CDV, BCV and tecovirimat are highly efficacious when used therapeutically and prophylactically. They are partially protective in moderate, but not severe, immunodeficiency models. Clinical trials consistently report BCV and tecovirimat to be safe and well tolerated in humans. In human case reports, CDV, BCV and tecovirimat contributed to recovery from orthopoxvirus infection. BCV and tecovirimat demonstrate strong synergistic effect and may reduce risk of antiviralresistant strains. Conclusion: BCV and tecovirimat are particularly promising as anti-smallpox agents. Gaps in the literature indicate that further research should focus on developing more robust immunodeficiency and antiviral-resistance models.

Is Australia ready for monkeypox?

“…Effective antivirals include tecovirimat and brincidofovir. 13 Cidofovir can also be used but is nephrotoxic. Vaccinia immune globulin is effective but has limited supply.…”

“…Vaccinia immune globulin is effective but has limited supply. 13 Epidemic control includes case finding, isolation of cases, contact tracing and ring vaccination. The risk to contacts is classified according to the kind of exposure and individual risk.…”

Monkeypox: From Past to Present Outbreak

“…The nephrotoxicity of cidofovir has been removed in the form of CMX-001 [6]. Numerous orthopoxvirus species have shown antiviral effectiveness when exposed to CMX-001 [66]. The medication ST-246 has shown efficacy against a variety of orthopoxvirus species, including the variola virus [66].…”

“…Numerous orthopoxvirus species have shown antiviral effectiveness when exposed to CMX-001 [66]. The medication ST-246 has shown efficacy against a variety of orthopoxvirus species, including the variola virus [66]. It prevents the release of the intracellular virus from the cell.…”

Poxvirus Driven Human Diseases and Emerging Therapeutics

“…Once diagnosed, treatment for monkeypox is largely supportive and symptomatic. There are no approved therapies for monkeypox but animal studies suggest cidofovir, tecovirimat and brincidofovir may have a role in treatment or lowering disease burden (57). Adler et al have reported successful clinical treatment of human Monkeypox with oral Brincidofovir in three cases -the dosing regimen was 200 mg as a single dose in one case and two doses in the other two cases.…”