Acyclovir for COVID-19
Acyclovir is not effective for treating COVID-19 and should not be used for this indication. Acyclovir is a nucleoside analogue specifically designed to target herpesvirus DNA polymerase and has no activity against SARS-CoV-2, which is a coronavirus with entirely different replication mechanisms 1.
Why Acyclovir Does Not Work
Wrong viral target: Acyclovir is specifically designed for herpes simplex virus (HSV) and varicella-zoster virus (VZV), which are DNA viruses. SARS-CoV-2 is an RNA virus with completely different enzymatic machinery that acyclovir cannot inhibit 1.
Explicit recommendation against use: Clinical guidelines from 2020 specifically state that antiviral drugs commonly used in clinical practice, including acyclovir, are invalid for 2019-nCoV (SARS-CoV-2) and are not recommended 1.
No mechanism of action: Acyclovir requires phosphorylation by viral thymidine kinase (present only in herpesviruses) to become active. SARS-CoV-2 lacks this enzyme entirely, rendering acyclovir completely inactive against COVID-19 1, 2.
What Actually Works for COVID-19
Based on the most recent high-quality guidelines, the following treatments have demonstrated benefit:
For Hospitalized Patients Not on Mechanical Ventilation
- Systemic corticosteroids are strongly recommended for patients requiring supplementary oxygen or ventilatory support 3.
- Remdesivir for 5 days should be considered in hospitalized patients with COVID-19 who do not require mechanical ventilation or ECMO 3.
- Anticoagulation is strongly recommended in hospitalized patients 3.
For Severe Disease
- IL-6 receptor antagonists (tocilizumab) are conditionally recommended for patients with hypoxemic respiratory failure 3.
- Extending remdesivir to 10 days should be considered for patients who require mechanical ventilation or ECMO within the initial 5-day course 3.
What to Avoid
- Do not initiate remdesivir in patients already on mechanical ventilation or ECMO at baseline, as it may increase mortality in this population 3.
- Lopinavir/ritonavir is not recommended due to lack of clinical benefit and significant adverse drug reactions 3.
- Hydroxychloroquine with or without azithromycin is not recommended due to lack of efficacy and potential for serious side effects including QT prolongation 3.
Common Pitfall to Avoid
Do not confuse acyclovir with remdesivir simply because both are nucleoside analogues. While they share a structural class, remdesivir was specifically designed to inhibit viral RNA-dependent RNA polymerase (present in coronaviruses), whereas acyclovir only works against herpesvirus DNA polymerase 1, 2. Using acyclovir for COVID-19 would provide zero antiviral benefit while potentially delaying appropriate treatment and exposing patients to unnecessary medication costs and potential adverse effects.