More than 20 different SARS-CoV-2 vaccines were tested and are currently in use. However, vaccine hesitancy still exists on a global scale, and breakthrough infections are frequent among vaccine recipients. Therefore, in the battle against COVID-19, developing specific antiviral drugs for SARS-CoV-2 is a top goal, especially with the rise of mutations that may partially evade neutralization by antibodies. A variety of SARS-CoV-2 inhibitors have already been reported. However, only few direct-acting antivirals, such as remdesivir, molnupiravir, and nirmatrelvir (Figure ), have been approved. Remdesivir is an intravenously administered RNA-dependent RNA polymerase (RdRp) inhibitor for COVID-19 infection, while molnupiravir is an orally available RdRp inhibitor used for the treatment of mild to moderate cases of COVID-19. It should be noted that remdesivir as well as molnupiravir are repurposed drugs. Nirmatrelvir, a peptidomimetic inhibitor of the SARS-CoV-2 main protease (M pro ), is commercialized under the brand name Paxlovid in combination with ritonavir to prevent its fast metabolic degradation. The cysteine protease M pro , crucial for virus replication, is highly conserved across coronaviruses but lacks a close homolog in humans. Following the approval of Paxlovid, numerous compounds that inhibit M pro have been reported. The SARS-CoV-2 virus is an enveloped positive-stranded RNA virus that exhibits remarkable genetic similarities to earlier coronaviruses, especially SARS-CoV-1, which first appeared in the Guangdong province, China, in 2002, and shares 79% of its genome. It is now acknowledged that these two coronaviruses have similar molecular mechanisms for recognizing, entering, and replicating in hosts. SARS-CoV-2 entry into host cells depends on the interaction between the receptor-binding domain of the spike glycoprotein (S) and the cellular receptor of the host, i.e., angiotensin-converting enzyme 2 (ACE2). The S1 and S2 subunits, which facilitate membrane fusion and attachment to host cells, are present in each monomeric unit of the S protein.