Treatment Strategies: Antiviral Treatments
As described briefly earlier, a number of studies have focused on repurposing existingantiviraltherapies, particularly those showing prior effectiveness against SARS-CoV and MERS-CoV. The most popular exploratory antiviral is the combination of lopinavir / ritonavir which appears in 34 investigational studies (Table 1: antivirals). Both drugs act as protease inhibitors, and are commonly used in HIV-1 management [57]. However, due to the rapid catabolism by the cytochrome P450 enzyme system (specifically 3A4 isoenzyme) [57], lopinavir has inadequate oral bioavailability for substantial therapeutic operation. Ritonavir is thus administered concomitantly to suppress this, greatly improving lopinavir’s half-life. In 2004, the efficacy of lopinavir / ritonavir against SARS-CoV was investigated and found to be effective compared with a historical control[58].Nevertheless, efficacy was not seen in a randomized open-label study (lopinavir / ritonavir versus standard care) in 199 COVID-19 patients (Clinical Trial Number: ChiCTR2000029308, recruitment target reported as 160 registry participants; Table 1). There was no majorgain in the overall mortality or viral load [59]. Remdesivir is a novel antiviral analog nucleotide, originally developed to treat the Ebola and Marburg viruses [10, 60]. Nonetheless, it does have efficacy against a number of pathogenic viruses, including both in vitro and in vivo models of SARS-CoV and MERS-CoV[10, 61]. Subsequent diagnosis of the first COVID-19 case and subsequent recovery in the U.S.[11], this molecule was of great interest. A number of globally reported trials are currently underway to examine theefficacy of COVID-19 (Table 1: Antivirals). Many other antiviral medications, especially those with action against various influenza subtypes and other RNA viruses are being studied. Which are favipiravir (T-705, Avigan), umifenovir (Arbidol), triazavirin (TZV), and marboxil (Xofluza) baloxavir. Most trials concentrate on medications widely used to treat RNA viruses, such as HCV and HIV. Which include danoprevir / ritonavir, azvudine, ledipasvir / sofosbuvir, sofosbuvir / daclatasvir, darunavir / cobicistat and emtricitabine / tenofovir (Table 1: antivirals). Additionally, 26 studies examine the efficacy of antiviral interferon-based drugs, and interestingly often look at various routes of administration (e.g., nasal).