**1. Introduction**

Coronaviruses (CoVs) belong to the subfamily Orthocoronavirinae in the family of Coronaviridae. In this family, there are four types of viruses: α-coronavirus, β-coronavirus, γ-coronavirus, δ-coronavirus [1]. The CoV genome is an enveloped, positive-sense, and single-stranded RNA, and it has the largest genome of known RNA viruses. It is known that α- and β-CoV types cause infections in mammals as δ- and γ-CoVs infect birds [2]. Severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) belonging to β-CoVs are the most

aggressive strains of coronaviruses and cause viral pneumonia outbreaks [3, 4]. SARS-CoV disease is a kind of pneumonia and caused by novel CoV whose genome structure was more than 82% identical to those of SARS-CoV, named coronavirus disease 2019 (COVID-19) [5, 6]. SARS-Cov-2 is a beta gene virus genetically very close to bat-CoVRaTG13, and bat-SL-CoVZC45 Covs can cause severe illness. As the COVID-19 outbreak turned into a global threat, the World Health Organization (WHO) announced it as a global pandemic on 12 March 2020. The COVID-19 pandemic has changed the scenario of the entire world. COVID-19 outbreak started in Wuhan, China, has globally spread to 219 countries and territories [7]. Currently, there are few vaccines for COVID-19. Their acceptance and efficacy are an issue of debate across the whole world. Therefore, there is an urgent need to find drugs or vaccines for the treatment of COVID-19 infections effectively. However, there are some studies related to the use of known drugs such as remdesivir and chloroquine that have proved efficacy on COVID-19 infection. We summarize some antiviral drugs as therapeutic options for the treatment of COVID-19 [8].

COVID-19 mainly attacks the respiratory-tract-associated organs. Additionally, the virus has shown impact various to other organs or systems such as the gastrointestinal system, nervous system, etc. [9]. The most common symptoms in COVID-19 patients are fever, dry cough, loss of taste, lethargy, shortness of breath, dyspnea, chest pain, fatigue, myalgia, whereas headache, dizziness, abdominal pain, diarrhea, nausea, and vomiting are less commonly observed [10, 11]. Anosmia is also one of the most critical symptoms in COVID-19 patients [12]. COVID-19 is more contagious than other coronaviruses, and its transmission rate is higher than the closely related strain, SARS-CoV-10 [13]. Currently, new variants of COVID-19 are reported from different regions of the world. Coronavirus interacts with cell surface receptors such as angiotensin-converting enzyme-2 (ACE-2) and neuropilin to gain entry inside the cell. The receptor-binding domain of viral spike protein is essential in SARS-CoV-2 entry into the host cell via surface ACE-2 [14]. Recently, another cell receptor Neuropilin-1 was found to be involved in SARS-CoV-2 entry. After binding to the receptor, the conformational change in the spike protein leads to virus fusion with the host cell membrane. The virus may transfer the RNA directly inside the cells or may proceed through the endosomal pathway [15]. Upon translation of viral RNA, the viral replicase polyprotein PP1a and PP1ab are produced and cleaved into small products by viral endopeptidase [16]. RNA-dependent RNA polymerase (RdRp) produces subgenomic RNAs by discontinuous transcription [16, 17]. This further gets translated into respective viral proteins. After processing through the endoplasmic reticulum (ER), ER-Golgi intermediate compartment (ERGIC), and Golgi complex, the viral RNA and proteins are assembled into virions. These virions are transported through vesicles and exocytosed for transmission. These steps of the viral life cycle are beneficial virus inhibition targets for different drugs. The coronaviruses are ribonucleic acid (RNA) viruses, which have a positive single-strand RNA [14, 18]. When SARS-CoV-2 enters the body and comes in contact with the host cell membrane, some changes occur in the structure of the virus. The human TMPRSS2 protein alters the conformation of the spike glycoprotein in the virus. Two substantial protease enzymes, 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLPro), have essential roles in its viral replication process after it enters the host cell via ACE2 receptors [19]. The expression of several genes, such as AHCYL2, ZNF385B, etc., appears to have a strong correlation with the expression of ACE2 and TMPRSS2 protein receptors in human healthy and normal lung cells [20].

#### *Antiviral Drugs and Their Roles in the Treatment of Coronavirus Infection DOI: http://dx.doi.org/10.5772/intechopen.101717*

However, repurposing drugs could prove to be beneficial tactics for finding COVID-19 treatment, including cost-effectiveness, elimination of some clinical trial steps, faster on-field availability, combining the drugs with other possible drugs, and the invention of information about the mechanisms of the existing drug. Researchers were able to develop the possible COVID-19 medications using information from previous CoVs therapies, genetic sequences, and protein modeling studies. Antimalarials, antivirals, antibiotics, and corticosteroids are among the most often studied medications, and they have been repurposed based on their ability to neutralize viruses, reduce lung inflammation, or alleviate other illness symptoms. Chloroquine (CQ ), hydroxychloroquine (HCQ ), and azithromycin (AZM) are the most often utilized antiviral drugs against COVID-19, since they have already demonstrated reasonable antiviral efficacy against SARS-CoV, MERS-CoV, and SARS-CoV-2. Anti-HIV medications lopinavir/ritonavir (LPV/RTV) are being studied for COVID-19 since they were successful in previous CoV epidemics. Furthermore, the anti-Ebola medicine remdesivir (RDV) was evaluated for COVID-19 and garnered further attention.

Similarly, favipiravir (FPV), ribavirin (RBV), umifenovir (UFV), and oseltamivir (OTV) have broad-spectrum antiviral activities and clinically tested against COVID-19. The effective uses of HCQ, RDV, LPV/RTV, or LPV/RTV in combination with Interferon (IFN) β-1a against COVID-19 [21], all these drugs had little or no effect on overall mortality, initiation of ventilation, and duration of hospital stay in hospitalized patients. So far, to treat severe and critical COVID-19, only corticosteroids have proven effective [21]. Other drugs, such as Angiotensin-Converting-Enzyme inhibitors (ACEi), have also been used to treat COVID-19. However, no clear correlation was reported between mortality rate and ACEi drugs in hypertension patients with COVID-19 [22]. Due to the possibility of secondary infection in these patients, antibiotics have been used as various protocols [23].

Umifenovir (UFV) may interact with SARS-CoV-2 surface glycoproteins and lipids and obstruct the interaction with the entry receptor ACE-2. Antibodies against SARS-CoV-2 may prevent the virus from entering the body and causing illness. Chloroquine (CQ ), hydroxychloroquine (HCQ ), and azithromycin (AZM) can raise endosomal pH, making viral entrance and RNA release more difficult. CQ, HCQ, and AZM all have immunomodulatory properties. RDV, FPV, and RBV are nucleoside inhibitors that impede RNA replication and reduce RNA-dependent RNA polymerase activity. Fraternization of LPV with viral protease may change proteolysis. OTV may interact with components involved in exocytosis, preventing the virus from leaving the cell. Antibodies against cytokine receptors and corticosteroids have been shown to have anti-inflammatory properties in the face of excessive immune responses. Drugs such as CQ are wide-spectrum inhibitors of viral cell entry, and RDV is a wide-spectrum RNA polymerase inhibitor. SARS-CoV-2 infection concurrently triggers the host immune system and an inflammatory cascade response (cytokine storm). These are being targeted in the treatment of COVID-19 patients [23].

So far, no fully effective drug has been discovered against this virus. The antiviral drugs, usually nucleoside analogs or intracellular proteases, block the virus by preventing its entry into the cell or by interfering with its replication inside the cell. Protease inhibitors target certain proteases, whereas fusion inhibitors block the fusion phase of viral entrance. Transcription inhibitors impede viral replication by inhibiting RNA-dependent RNA polymerase during the reverse transcription process. Nucleoside reverse transcriptases are some of the transcriptase inhibitors. M2 channel protein is a target for certain antivirals. In this chapter, we have provided information

about repurposed drugs that are used against COVID-19, the mechanism of activity, therapeutic regimens, pharmacokinetics, and drug-drug interactions [7, 8].
