Overview

The recently emerged Covid -19 infection has spread rapidly across the world and evolved into a pandemic. The virus has infected millions of people worldwide and has taken over numerous lives across countries. Healthcare professionals worldwide are working to discover new therapeutic options that can help COVID-19 patients. Based on the research, doctors and scientists have classified various classes of drugs like remdesivir, hydroxychloroquine, ritonavir or lopinavir, and ribavirin as effective treatments for COVID-19 patients.

What are the Potential Therapeutic Options for COVID-19 Patients?

As of now, the majority of the therapeutic options available for COVID-19 patients are meant for prevention of complications such as organ failure and giving supportive care. Scientists and doctors are giving their best efforts to discover therapeutic options for COVID-19 patients. These therapeutic options are divided into two categories, that include:

• Researching on available agents that can have an anti-viral effect on COVID-19
• Development of new agents that help specifically target the coronavirus and other host factors

Available Agents

To develop a new drug for COVID-19 and get approval for it to be used on humans may take several years. With the current situation, waiting for several years may cause more damage. So, scientists are trying to repurpose already available anti-viral agents that have effectively been used to treat other viral infections and diseases. This may be a good therapeutic option because pharmacokinetics and pharmacodynamic properties, dosages, and side effects of these anti-viral agents are already known. Various categories of drugs have been classified to help treat COVID-19. These are:

1. Directly acting antivirals
2. Host-targeting antivirals
3. Immune-suppressive or immune-modulatory treatments
4. Biological therapies

1. Directly acting anti-virals. Directly acting antivirals include, remdesivir, HIV-1 protease inhibitors, and other drugs, such as favipiravir, baloxavir, and triazavirin.

Ribavirin is a broad-spectrum anti-viral drug. It has exhibited moderate anti-viral activities against the SARS-CoV infection. However, some studies found out that the drug had no significant effect on the replication of SARS-CoV.

Remdesivir, used against Ebola and Marburg viruses, is a nucleotide analog RNA-dependent RNA polymerase (RdRp) inhibitor. This drug has broad-spectrum anti-coronavirus activity as it has been effective in treating against the human and zoonotic viral infections in the past.

Another potential candidate for the treatment of COVID-19 is HIV-1 protease inhibitors. These include nelfinavir, saquinavir, emtricitabine/tenofovir, darunavir/cobicistat, and azvudine. Nelfinavir has been effective in inhibiting the replication of the coronavirus in vitro.

Other anti-viral drugs such as baloxavir, favipiravir, triazavirin, danoprevir/ritonavir, and marboxil are being studied as well. These drugs have been successful in the treatment of many influenza subtypes and hepatitis C virus infections. A study reported that danoprevir/ritonavir provided relief from the COVID-19 symptoms in many patients.

2. Host-targeting anti-virals. Traditional antimalarial drugs such as chloroquine and hydroxychloroquine have proven to be effective against the replication of the coronavirus in vitro. These medications work by providing defense against the entry of the virus and its further replication. A few small studies and one subjective report revealed the effectiveness of these drugs against the coronavirus infection.

3. Immune-suppressive or immune-modulatory treatments. A protein called interferon helps in restoring the innate immune responses in the host cells of the body. They have also been effective in inhibiting the replication of the coronavirus. Combining interferons with other anti-viral drugs such as lopinavir/ritonavir or ribavirin has effectively treated MERS and SARS in the past .

Scientists believe that the severity of COVID-19 may be related to an excessive inflammatory response called the cytokine storm. This will make immune-suppressive and immune-modulatory agents like intravenous immunoglobulin and corticosteroids a potential therapeutic candidate for COVID-19 treatment.

4.  Biological therapies. This therapeutic option has been successful in treating MERS and SARS and can be a potential candidate for COVID-19 patients as well.

Development of New Agents

Along with the already available potential treatment options, the development of new anti-viral agents that specifically target the coronavirus should be considered as well. It is believed that these may have better anti-coronavirus activity theoretically. However, they need to be first evaluated in animal trials and then human trials, which could take several years.

The anti-viral agents will target:

• Viral nucleic acids
• Structural proteins
• Host-dependent targets

1. Viral nucleic acids. Drugs that target nucleic acids show  broad-spectrum activities. These drugs can target several types of viruses. An inhibitor called mycophenolate mofetil has shown effective anti-viral activities against MERS.

2. Structural proteins. There are two functional subunits called S1 and S2 in the coronavirus spike glycoprotein. These subunits are responsible for pathogenesis, tissue-tropism, and cell-receptor binding of viruses. When designing vaccines and therapeutics, these subunits are the primary target.

3. Host-dependent targets. Host factors that play an essential role in the life cycle of the viruses have been identified as targets of anti-viral agents. A small inhibitor in the form of a molecule, N-(2-aminoethyl)-1-aziridine-ethanamine, is believed to inhibit the viral fusion’s catalytic activities with the human cells.

Another potential therapeutic option for COVID-19 is host cell signalling pathways. Phosphoinositol 3-kinase/serine-threonine kinase/mammalian target of rapamycin (mTOR) signalling responses have been known to play significant roles in treating MERS-Coronavirus infection. Some recent studies showed that combining the mTOR pathway with AMP-activated protein kinase might help control the onset of hyper inflammation, cell injury, oxidative stress, and mitochondrial dysfunction. This makes targeting the mTOR pathway to be an effective anti-viral drug therapy in the treatment of COVID-19.