# An Update of Carbazole Treatment Strategies for COVID-19 Infection
## 3 Different COVID-19 Treatments  
In March 2020, he WHO declared the outbreak of COVID-19 as a pandemic, and several drugs used at the beginning proved useless in fighting the infection [6; 7]. Lately, there has been the approval of some new-generation drugs for the clinical treatment of severe and critical COVID-19 symptoms. Nevertheless, more medications are required to attenuate the pandemic impact [5]. Many of the employed therapeutic approaches since the start of the pandemic were shown to be ineffective against the virus. So, the identification of drugs to be used effectively for the treatment of COVID-19 is strongly needed [18; 19; 20]. COVID-19 is considered to be a multisystem disease, and its pathogenesis involves severe lung inflammation and immune deficiency linked to inadequate immune response and enhanced cytokine production. Therefore, therapeutic approaches currently being studied concern antiviral and anti-proinflammatory cytokines, anti-infective and life support treatments, monoclonal antibodies, and passive immunotherapy, mostly in people with severe disease [21]. The antiviral treatments used so far for SARS-CoV-2 virus can be presented into two categories [22; 23]:  
1. Agents that target the virus proteins: S protein and viral proteases or virus RNA which are the main viral targets. 2. Agents that target host proteins that allow the virus to enter the cell, such as the enzyme ACE-2, TMPRSS2 (transmembrane protease serine 2), furin, and cathepsin-L, the proteins which can promote the attachment of viral cells such as HSPG (heparin sulfate proteoglycans), eukaryotic translation proteins such as S1R (endoplasmic reticulum chaperone protein), and transcriptional system proteins such as inosine monophosphate dehydrogenase and dihydrorotate dehydrogenase [22; 23]. Several studies and laboratory works are still in demand to discover new and effective antiviral drugs against SARS-CoV-2. These studies could deal with the following areas [23]:  
1. Inhibitors that block the virus from entering the human cell: 1. S Protein inhibitors: plasma from convalescing infected persons, miniproteins, monoclonal antibodies, nanocods, soluble human ACE-2 protein; 2. Fusion entry inhibitors; 3. inhibitors of TMPRSS2, such as nitazoxanid, camostat, nafamostat, gabexat, dutasteride, bromhexine, niclosamide, and provalutamide; 4. Endosomal entry inhibitors: NIP1 inhibitors (EG00229), niclosamide, hydroxychloroquine, umifenovir, nitazoxanide; furin inhibitors (dec-RVKR-cmk); cathepsin L inhibitors (teicoplanin, SSAA09E1, K1777); 5. Inhibitors of HSPG (lactoferrin). 2. Viral proteases inhibitors: inhibitors of Mpro, the main protease of the virus (lopinavir/ritonavir, PF-07321332, PF-07304814, GC376, carprofen (**1**, Figure 1)); viral papain-like protease inhibitors (PLpro). 3. Viral RNA inhibitors, RNA-dependent RNA polymerase (RdRp) inhibitors (ATCC27, remdesivir, molnupiravir, favipiravir), host protein inhibitors that support the synthesis of viral RNA (dihydroorarate dehydrogenase inhibitor (PTC299), inosine monophosphate dehydrogenase inhibitor (merimepodib). 4. Host protein inhibitors that support the synthesis of viral protein: S1R agonists (fluvoxamine); inhibitors eEF1A (plitidepsin). 5. Viral immunomodolution inhibitors: host \(\alpha/\beta\) importin inhibitors (ivermectin). 6. Agents that support natural host immunity: interferons [23]. Previous studies to develop anti-virus SARS-CoV-2 therapies relied on the design of medicaments that obstruct the viral life cycle, so: (1) the inhibition of viral entry into the cell by blocking the spike protein and/or ACE2; (2) the inhibition of viral proteases; (3) the prevention of viral replication via the RNA dependent viral RNA polymerase (RdRp) inhibition [24]. Much of this research is based on the medicaments reuse strategy to find new therapies from already adopted drugs, speeding up like this the drug discovery process and providing the benefit of instant use of medicaments that have previously proven safety safe [25].