Current challenges in the discovery of treatments against Mayaro fever

ABSTRACT

Introduction

Mayaro fever is an emerging viral disease that manifests as an acute febrile illness. The disease is self-limiting, however joint pain can persist for months leading to chronic arthralgia. There is no specific treatment available, which ultimately leads to socioeconomic losses in populations at risk as well as strains to the public health systems.

Areas covered

We reviewed the candidate treatments proposed for Mayaro virus (MAYV) infection and disease, including antiviral compounds targeting viral or host mechanisms, and pathways involved in disease development and pathogenicity. We assessed compound screening technologies and experimental infection models used in these studies and indicated the advantages and limitations of available technologies and intended therapeutic strategies.

Expert opinion

Although several compounds have been suggested as candidate treatments against MAYV infection, notably those with antiviral activity, most compounds were assessed only in vitro. Compounds rarely progress toin vivo or preclinical studies, and such difficulty may be associated with limited experimental models. MAYV biology is largely inferred from related alphaviruses and reflected by few studies focusing on target proteins or mechanisms of action for MAYV. Therapeutic strategies targeting pathogenic inflammatory responses have shown potential against MAYV-induced disease in vivo, which might reduce long-term sequelae.

KEYWORDS:

• Antiviral compounds
• arthritogenic disease
• candidate treatments
• compound screening technologies
• immunopathogenesis
• infection models
• mayaro virus

Article highlights

• Mayaro virus is an emerging arbovirus associated with arthritogenic disease in humans.

• There are no antiviral compounds or specific treatments available against Mayaro fever.

• Anti-MAYV compounds have been discovered but never advanced to preclinical drug development or clinical testing.

• Mechanistic insights and target validation are lacking in drug discovery against MAYV, the use of cutting-edge technologies is desirable.

• Structural and biological differences between MAYV and other alphaviruses suggest specificity and indicate that more research on MAYV is necessary.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

We would like to thank Eduardo H. Salviano Bezerra for his assistance with Figure 3 preparation.

Additional information

Funding

This work was supported by the São Paulo Research Foundation (FAPESP) via grant 2022/03645-1 for MLN and 2021/05519-0 for REM. MLN was also supported by INCT Dengue Program grant 465425/2014-3, and by INCT Viral Genomic Surveillance and One Health grant 405786/2022-0. MLN and REM are Brazilian National Council for Scientific and Technological Development (CNPq) Research Fellows. MLN and NV are partly funded by the Centers for Research in Emerging Infectious Diseases (CREID), “The Coordinating Research on Emerging Arboviral Threats Encompassing the Neotropics (CREATE-NEO)” grant U01AI151807 (to NV) by the National Institutes of Health (NIH/USA).