- Brand Name: Kaletra
- Indication: treatment of HIV-1
- Class: protease inhibitor and cytochrome p450 (CYP450) inhibitor
- Mechanism: ritonavir inhibits CYP450 to increase the amount of lopinavir in the blood (reduce the clearance of lopinavir from the body). Lopinavir inhibits the protease enzyme of HIV which is responsible for the replication and growth of the virus. Lopinavir/ritonavir may bind to a key enzyme involved in coronavirus replication
- Common adverse events (AEs): Gastrointestinal (GI) events (i.e. nausea and vomiting)
- Drug-Drug interactions: CYP3A inhibitors, tadalafil, riociguat, vorapaxar, fusidic acid, salmeterol, rivaroxaban (significant drug interactions)
- Safety and Efficacy: Clinical evidence of safety and efficacy is limited. Study found that there was no difference in clinical improvement or mortality compared to standard treatment in severe COVID-19 patients. This medication has unfavorable pharmacodynamics in treatment of COVID-19 as shown by clinical trials. This medication comes with a risk of irregular heartbeat especially in patients with severe COVID-19 with comorbidities. 

Lopinavir/ritonavir

- Brand Name: Veklury
- Indication: treatment broad spectrum RNA viruses (initially Ebola and Marburg treatment but was not effective enough)
- Class: RNA dependent RNA polymerase (RdRp) inhibitor, Nucleoside analogue
- Mechanism: this drug has a similar structure to nucleosides found in RNA and is incorporated into the RNA produced by the virus using RdRp and stops its synthesis. It competes with ATP to be incorporated into growing viral RNA. It also avoids viral defense against nucleoside analogues by not terminating the RNA chain immediately.  
- Common AEs: Liver events
- Drug-Drug Interactions: lower risk with remdesivir rapid clearance
- Safety and Efficacy: Combination therapies of this medication with chloroquine may be effective against COVID-19 according to preclinical trials. This medication has shown some promising results in treatment of COVID-19 in the US. Data from clinical trials has shown remdesivir to shorten recovery time in hospitalized COVID-19 patients. It worked best when treatment is given early on in the illness.

Remdesivir

- Brand Name: Avigan (Japan),  Avifavir (Russia), Favilavir (China)
- Indication: treatment of influenza virus infections and other RNA viruses including arenavirus, bunyavirus and filovirus
- Class: RdRp inhibitor
- Mechanism: RdRp is overexpressed in many RNA viruses and this medication, when activated in enzymes in the body inhibits RdRp dependent enzymes
- Common AEs: GI events, psychiatric events, increased serum uric acid, abnormal liver function test results, chest pain
- Drug-Drug Interactions: N/A
- Safety and Efficacy: Studies have shown faster recovery from COVID-19 symptoms. In comparison to lopinavir/ritonavir, favipiravir resulted in faster clearance of the virus from the body. In comparison to standard care there was faster viral clearance. This medication cannot be used during pregnancy due to teratogenic and lethal effects on the developing embryo seen in preclinical animal studies. 

Favipiravir

- Brand Name: Prezcobix (US), Rezolsta (EU)
- Indication: HIV-1 treatment
- Class: protease inhibitor, CYP450 inhibitor
- Mechanism: Darunavir inhibits the HIV-1 protease from forming a dimer and becoming active. Cobicistat inhibits the activity of CYP450 3A to increase the amount of darunavir in the blood. The drug ultimately inhibits the maturation of the virus. 
- Common AEs: GI adverse events (nausea, vomiting), headache
- Drug-Drug Interactions: Colchicine and strong inhibitors of CYP3A and P‐glycoprotein
- Safety and Efficacy: Preclinical studies showed the treatment had an inhibitory effect in COVID-19. This combination of medications was well tolerated in COVID-19 patients. A clinical trial showed that viral clearance when treated with darunavir/cobicistat was comparable to the control, in which patients received no oral antiviral medication, and did not seem to increase the amount of negative test results for COVID-19 after treatment. 

Darunavir/cobicistat

- Brand name: Fusan (nafamostat) and Foypan (camostat) (Japan)
- Indication: treatment of chronic pancreatitis and postoperative reflux of stomach acid back up into the esophagus
- Class: Serine protease inhibitors
- Mechanism: Camostat mesilate inhibits the enzymatic activity of TMPRSS2, a protease that divides the S2 subunit of the viral S protein of SARS-CoV-2 and is thus essential for cell entry of the virus. Nafamostat inhibits S protein initiated membrane fusion by targeting MERS-CoV and thus it may inhibit the coronavirus from entering the cell.
- Common AEs: Skin rashes, itching, GI events (nausea, abdominal pain) and changes in liver enzymes
- Drug-Drug Interactions: N/A
- Safety and Efficacy: The drugs seem well tolerated and can be used alone or in combination with other antivirals. Nafamostat significantly decreased S protein initiated membrane fusion between the virus and cell at low concentrations.

Camostat mesilate and Nafamostat

- Lopinavir/ritonavir
- Remdesivir
- Favipiravir
- Darunavir/cobicistat
- Camostat mesilate and nafamostat

Rutgers University

COVID-19 currently has multiple treatment options for infected patients from existing medications that are being repurposed for COVID-19. This generally consists of antiviral medications or anti inflammatory drugs. It is essential to explore the properties of and actions of the drug in the body of COVID-19 patients. The use of these drugs will be affected by their disease state, thus impacting the efficacy and/or safety of these medications. As a result drug therapies may have to be monitored for adverse reactions especially considering patients will likely be on multiple medications at once, posing a risk for drug-drug interactions. A pharmacological analysis is necessary to determine the best and safest option for managing COVID-19 with medication.

Current pharmacological treatments for COVID-19: What's next? 

Antiretroviral Agents

- Tocilizumab
- Chloroquine/Hydroxychloroquine
- Colchicine
- Baricitinib
- Aviptadil
- Eculizumab
- Azithromycin
- Anakinra
- Pentoxifylline
- Theophylline
- Cyclosporine

Immunomodulatory and Anti inflammatory Agents

- Camrelizumab
- Bevacizumab
- Thalidomide

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