Artemisinin is an anti-inflammatory phytomedicine with broad-spectrum antiviral activity. Artemisinin and its antimalarial properties were discovered by the Chinese scientist Tu Youyu, who became one of the laureates of the 2015 Nobel Prize in Physiology or Medicine for this breakthrough in tropical medicine. It is a commonly used anti-malaria drug. Artemisinin has recently been repurposed as a potential COVID-19 drug. Its documented anti-SARS-CoV-2 activity has been attributed to its ability to inhibit spike-protein mediated and TGF-β-dependent early steps in the infection process as well as its ability to disrupt the post-entry intracellular events of the SARS-CoV-2 infection cycle required for viral replication. In addition, Artemisinin has anti-inflammatory activity and reduces the systemic levels of inflammatory cytokines that contribute to cytokine storm and inflammatory organ injury in high-risk COVID-19 patients. We postulate that Artemisinin may prevent the worsening of the health condition of patients with mild-moderate COVID-19 when administered early in the course of their disease.

Our COVID-19 drug candidate ARTIVeda™/PulmoHeal is a novel gelatin capsule formulation of the Artemisia extract Ayurveda for oral delivery of TGF-β targeting anti-malaria phytomedicine Artemisinin with documented anti-inflammatory and anti-SARS-CoV-2 activity. Here we report the safety and efficacy of ARTIVeda™ in adult COVID-19 patients with symptomatic mild-moderate COVID-19, who were treated in a randomized, open-label Phase IV study in Bangalore, Karnataka, India (Clinical Trials Registry India identifier: CTRI/2020/09/028044). ARTIVeda showed a very favorable safety profile, and the only ARTIVeda-related adverse events were transient mild rash and mild hypertension. Notably, ARTIVeda, when added to the SOC, accelerated the recovery of patients with mild-moderate COVID-19. While all patients were symptomatic at baseline (WHO score = 2-4), 31 of 39 (79.5%) of patients treated with ARTIVeda plus SOC became asymptomatic (WHO score = 1) by the end of the 5-day therapy, including 10 of 10 patients with severe dry cough 7 of 7 patients with severe fever. By comparison, 12 of 21 control patients (57.1%) treated with SOC alone became asymptomatic on day 5 (P=0.028, Fisher’s exact test). This clinical benefit was particularly evident when the treatment outcomes of hospitalized COVID-19 patients (WHO score = 4) treated with SOC alone versus SOC plus ARTIVeda were compared. The median time to becoming asymptomatic was only 5 days for the SOC plus ARTIVeda group (N=18) but 14 days for the SOC alone group (N=10) (P=0.004, Log-rank test). These data provide clinical proof of concept that targeting the TGF-β pathway with ARTIVeda may contribute to a faster recovery of patients with mild-moderate COVID-19 when administered early in the course of their disease.