Anti-CMV therapy, what next? A systematic review

Area of Science:

• Virology
• Infectious Diseases
• Pharmacology

Background:

• Human cytomegalovirus (HCMV) causes severe complications in immunocompromised individuals and congenital infections.
• Current HCMV treatments targeting viral polymerase face toxicity and resistance issues.
• Emerging antivirals like maribavir and letermovir offer improved management but do not fully address all needs.

Purpose of the Study:

• To review existing and novel molecules effective against HCMV.
• To highlight agents with direct or indirect antiviral activity.
• To identify potential new therapies for multidrug-resistant and congenital HCMV infections.

Main Methods:

• Literature review of molecules with demonstrated anti-HCMV activity.
• Analysis of direct-acting antivirals, natural compounds, and immunomodulating agents.
• Examination of preclinical and clinical data, including mechanisms of action and resistance.

Main Results:

• Direct-acting antivirals include brincidofovir, cyclopropavir, and benzimidazole analogs.
• Natural compounds like artemisinin derivatives, quercetin, and baicalein show indirect anti-HCMV effects.
• Immunomodulating agents (leflunomide, everolimus) and anti-CMV immunoglobulins also exhibit potential.

Conclusions:

• Multiple molecules show promise for HCMV treatment and prevention, alone or in combination.
• Novel approaches, including natural products and immunomodulation, warrant further clinical investigation.
• Addressing multidrug resistance and congenital HCMV remains a critical unmet need.