# SARS-CoV-2 Treatment: Current Therapeutic Options and the Pursuit of Tailored Therapy
## 7 Other Antivirals  
Several compounds have been examined and new trials have been launched to improve COVID-19 treatment.  
Favipiravir (FPV), the prodrug of a purine nucleotide, inhibits the RNA polymerase (Tables 2 and 3). On April 2020 there was lack of empirical evidence about favipiravir effectiveness against SARS-CoV-2, although it was described as having clinical efficacy for moderate COVID-19, compared with arbidol [23].  
A clinical study--albeit one that was not randomized, not double blinded and not placebo controlled--documented that FVP improves chest imaging, inducing a shorter viral clearance time [24].  
In a multicenter, randomized controlled study performed in COVID-19 patients randomized into CQ and FPV groups, [PERSON] et al. [68] documented a lower duration of hospitalization in FVP-group vs. CQ-group.  
\begin{table}
\begin{tabular}{c c c c c} \hline \hline  & **Effect of the** & **Mechanism of** & **Selection of Drugs Affected** & **Clinical Comment** \\  & **Combination** & **Interaction** & & Risk for adverse events, \\  & & & & potential risk of \\  & & & & serotonin syndrome; \\  & & & & co-administered \\ CYP2D6 & & CYP2D6 & antiagonists, & The coadministration of \\ substrates & & chloroquine and hydroxylatione [4, 40, 57] & inhibition & antidepressants, & protease inhibitors and \\  & & & antipsychotics, codeine, & class IC \\  & & & antiarrhythtomic drugs (often & antiarrhythtomic is not \\  & & & class I) & recommended, whereas \\  & & & & in the other cases \\  & & & & caution is \\  & & & & needed [12, 65] \\ \hline CYP2C9 and & Serum level,by & & & & \\ CYP2C19 & lopinavir/ritonavir & CYP2C9 and CYP2C19 & & Phenyltoin, sulphonymous & Risk for reduced \\ substrates & [28, 47] & & induction & efficacy. \\ \hline  & & & & methylprednisolone, \\  & & & dexamethasone, (with possible \\  & & & oral glucocorticoid withdrawal \\  & & & syndrome), atorvastatin, \\ CYP1A2, 2C9, & Serum level,by & & IL-6 mediated & calcium channel blockers, \\
2C19 and 3A4 & & reduction in the & theophylline, warfarin, \\ substrates & & enzymes’ expression & phenprocovom, phenytoin, \\  & & & ciclosporin, benzodiazepepines, \\  & & & some anticancer drug (i.e., \\  & & & vincristine), antipsychotics & \\ \hline  & Serum level/by & & Protease inhibitors, digoxin, \\ P-gp substrates & chloroquine, hydroxy- & & & \\ chloroquine [4, 39] and & & & antitumor drugs, calcineurin \\  & lopinavir/ritonavir [28, 47] & & inhibitors, mTOR inhibitors & Risk for adverse events. \\ \hline  & Serum level,by & & & \\  & dexamethasonehesone [42] & & & \\ \hline UGT substrates & Serum level,by & & & \\  & ritonavir & UGT induction [65, 67] & Canagliflozin & Risk for reduced \\ \hline  & & & & \\ \hline  & & & & \\ \end{tabular} Data reported can be found in SmPC.; \(\uparrow\), increased; \(\downarrow\), decreased. \({}^{5}\) Interactions with remdesivir seem not to be significant, whereas the combination with lopinavir/ritonavir could be affected by interactions [28, 47]. \({}^{*}\) Among statins, pravastatin has less interactions. Lopinavir can worsen myalgia [65].  
\end{table}
Table 4: _Cont._In contrast, a recent single center observational study comparing IFN-based therapy (interferon \(\beta\)-1b, ribavirin, and lopinavir/ritonavir) vs. FPV in 222 non-critical hospitalized COVID-19 patients documented that IFN-based therapy was associated with a lower 28-day mortality vs. FPV (6 (9%) vs. 18 (12%)), without a difference in hospitalization duration [69].  
Other phase 3 clinical trials, which are ongoing, are evaluating the effect of FVP in COVID-19 (e.g., NCT04336904, NCT04558463, NCT04349241, NCT04600895).  
Common ADRs include gastrointestinal symptoms, decrease of neutrophil count, increase of transaminases, psychiatric symptom reactions, increase in blood triglycerides and uric acid elevations.  
Umiferonovir, ribavirin, oseltamivir, darunavir, camostat mesylate, nitazoxamide are being tested and need further analysis in order to determine their real efficacy [23; 70].