2. Discussion and Concluding Remarks
The new emergence of such a deadly virus needs potential agents to control it. It can be noted that mass vaccination is not easily affordable in many developing and underdeveloped countries immediately or before 2024 
. Additionally, over-populated countries might face some critical situations to ensure vaccines for all people due to vaccine insufficiency, and it might take longer to eradicate the outbreak. Moreover, the delta variant of concern has shown to be several times more resistant against vaccine-induced immunity 
. This crucial situation calls for effective treatment tools/antiviral agents to fight against the deadly infectious disease. This review mainly focuses on the efficiency and adverse effects of repurposing antiviral drugs potentially used to treat COVID-19.
Various drugs are being used as repurposing drugs, as there is no drug or effective treatment strategy against COVID-19. Therefore, the most promising seven antiviral drugs were taken under consideration to evaluate their efficacy and also their adverse effects in various levels of COVID-19 patients.
The very first drug and most widely used one was RDV. Though several studies mentioned above showed reduced mortality, shorter hospital stay, and better improvement of symptoms, several studies have been reported it to be insignificant in the case of COVID-19 patients’ recovery. Notably, the Macaque experiment stated that RDV was only efficient in viral clearance from the lower respiratory tract, not the upper one 
. Another randomized controlled study conducted by Wang et al. 
suggested no efficacy of RDV on the respiratory tract, neither upper nor lower. We can conclude by evaluating the above data that RDV might be effective for severe patients in mitigating the fatality rate and improvement of clinical conditions. The WHO has recommended RDV against in non-severe patients, which might match with the current findings.
FPV has shown great efficacy in this crucial situation, yet it is not patient-friendly due to its high dose. The studies discussed above revealed that FPV is a potential cure for COVID-19, both in severe and mild cases. Chen et al. 
reported a positive effect of FPV compared to ARB, as the former showed better improvement of symptoms like cough, pyrexia, and difficulty breathing. The drug is beneficial in alleviating symptoms, reducing viral load and hospital stay, but still, it is considered risky due to severe side effects like teratogenicity and embryotoxicity 
. This drug was very effective against H1N1 virus, which is also an RNA virus and has shown potential antiviral effects, perhaps most efficient in viral clearance. There has been no toxicity detected for its huge loading dose, but some adverse effects have been reported; cardiovascular complications, nausea, vomiting, diarrhea, and kidney injuries are the common ones. Several studies also compared the efficacy among FPV, hydroxychloroquine, chloroquine, and IFN, which had minimal significant difference. LPV/RTV combination was also a drug of choice for COVID-19 in the early stages of the pandemic. However, this combination proved to be insignificant in most of the cases studied, with some exceptions. The combination rather became the reason behind serious complications like diarrhea, gastrointestinal disturbance, electrolyte imbalance, and severe acute kidney injury in patients with both severe and mild COVID-19.
INF therapy is one of the promising treatments for COVID-19 now. Several subcategories of INF are known, such as IFN-alpha 1a, IFN-alpha 1b, IFN-beta 1a, IFN-beta 1b, IFN-gamma, and IFN-lambda. All have shown a variety of efficacy without severe side effects. They have worked to the betterment of patients’ condition and reduced the fatality rate among severe patients. Several studies were also carried out to evaluate and compare the potentials of these variants. Recombinant IFN has proven to be more potent than traditional ones. An efficient therapy known as triple therapy is a combination of IFN/LPV/r/RBV that has shown amazing results. Type I interferons (IFN-I, IFN-α, and IFN-ß) are immunomodulatory drugs that can induce antiviral effects and may induce pro-inflammatory activity, which has turned out to be beneficial for early treatment of COVID-19 
. Combination with other antiviral agents may mitigate the adverse effects as well as improve the clinical condition of the patients.
ARB has shown noteworthy effects in alleviating symptoms of COVID-19 and shortening the time for converting the PCR result from positive to negative. The potential antiviral agent works well both alone and in combination with various other agents like HCQ, RBV, and IFN. Antibiotic therapy alongside ARB is just the icing on the cake, showing prompt activity in quick recovery and reduction of fatality rate. It has proved to be more efficacious than other drugs like LPV/RTV and HCQ. All these have made it a potential agent in this pandemic situation. We can add oseltamivir to this list, but the drug showed great positive effects in severe patients when used early. Darunavir is emerging as a potent antiviral drug by lowering the mortality rate and hospital stay, but more studies are required to extensively verify its safety profile.
HCQ, LPV/RTV, and many other drugs, which were thought to be a treatment option earlier, are already banned by the WHO. FPV, ARB, and oseltamivir are in the pool of acceptable drugs for COVID-19, but there are still many randomized trials going on to assess their safety profiles. RDV is recommended in severe conditions considering its adverse effects that require limited use of the drug. Boosting the immune system is believed to be beneficial, so IFN type I might exert immunomodulation through its antiviral effects by stimulating interferon-stimulated gene (ISG).
As patients with COVID-19 might face multiple pathological dysfunctions, they must be prescribed multi-drug therapies 
. Moreover, several pieces of evidence have demonstrated that combination therapy is superior to monotherapy, as the multiple drugs might heal by acting on multiple receptors 
. Particularly, combination therapy in COVID-19 has become an excellent choice to wrestle against the disease. Several diagnoses revealed that secondary infections have become of paramount importance as an after-effect of COVID-19, and have some saddening consequences. A combination of potential antivirals with antibiotics is used to fight the secondary infections produced due to lessened immunity, along with the viral infection 
. Interferon uses an immunomodulator that has served well for COVID-19, and its combination with antiviral agents gives the best results. Moreover, the combination lowers the time taken to reduce viral shedding significantly 
. The mechanism could be the dual action of antivirals and immunomodulatory agents; one weakens the virus, and the latter strengthens the immunity so the body can recover faster, through confirmation or justification of this mechanism is yet to be provided. However, to define the exact mechanism and efficacy profile of the stated combinations in the current review, more precise investigation with larger data and evidence might be required.