Diagnosis and treatment of novel Coronavirus 2019 (COVID-19): A comprehensive review of the current literature

Coronavirus disease 2019 (COVID-19) is a pandemic caused by the novel coronavirus 2019. The rapid deployment of effective therapeutics is a high priority for researchers as there is still no specific medication and vaccine to treat the disease. Researchers worldwide are working and sharing their contribution regarding epidemiology, prevention, treatment, clinical and diagnostic patterns of the COVID-19. Current review is another contribution to the current literature, presenting the diagnosing techniques, effectiveness of medications that could be most appropriate therapeutic options for patients of SARS-CoV-2.

Earlier, coronaviruses three epidemic episodes has been reported, (1) sever acute respiratory syndrome (SARS) coronavirus, that had a little impact on global mortality and morbidity with more than 774 deaths, (2) Middle East respira-tory syndrome (MERS)coronavirus, that had originated in Saudi Arabia, (3) the SARS-CoV-2, that appears in December 2019, spread out pandemic, infected more than 19

Remdesivir
Remdesivir also known as GS-5734 is an antiviral agent that was designed for the treatment of Ebola and Marburg disease. This drug is a prodrug and when it metabolizes in the body then it makes a nucleotide analogue that is adenosine triphosphate that targets the viral Deoxyribonucleic acid (DNA) and Ribonucleic acid (RNA) polymerase [13].
Remdesivir was found to have no toxicity in the human body because this drug selectively targets the polymerases and therefor only targets the viral polymerase [14].

Neuraminidase inhibitor
There is no data suggesting the use of neuraminidase inhibitory agents for Covid-19 because this virus don't utilize neuraminidase and therefor there is no any enzyme which is inhibited by these inhibitors. Oseltamivir which is a neuraminidase inhibitory molecule has been approved for influenza A and B treatment. This drug inhibits the release of viral particles from host cell by blocking the neuraminidase of virus (20). Oseltamivir and baloxavir both have antiviral activity against influenza. But once influenza has been ruled out then these agents should be avoided for Covid-19. There is no any mechanism or data suggesting the use of neuraminidase inhibitors in coronavirus patients [13]. Corticosteroid therapy Lung infection causes inflammation of lungs which cause injury of lungs and therefor to prevent from lung inflammation corticosteroid therapy is used but its use also increases the risk of secondary infection which increases the timing of cleansing of virus. Use of corticosteroid for patients of corona is not clear because different analysis shows different results [26]. According to one of data use of corticosteroid has decreased the mortality rate in critically ill patients [27] while in others worst outcome has been seen with the patients receiving steroids and even delayed the clearance of virus [28]. According to a recent data decrease in the rate of mortality has been seen in SARS-CoV-2 patients who were receiving corticosteroids suggested a decrease in mortality in patients with ARDS with the receipt of corticosteroids [18].Careful consideration is required for the dosage of corticosteroid for Covid-19 and the ratio of risk and benefit should be checked for each individual patient. According to a statement from Chinese Thoracic Society a lower dose of ≤0.5-1 mg/kg/day of methylprednisolone for ≤7 days is prescribed in selected patients by measuring the ratio of risk and benefit [29].

Peptide (EK1)
The HCoVs enters host cell through its S protein. This S protein is transmembrane glycoprotein and is common in all human coronavirus. This S protein consist of two subunits: S1 and S2. This virus binds with host membrane through RBD (receptor binding domain) of S1 resulting conformational change in S2 and fusion peptide is inserted into host cell membrane. S2 subunit contain heptad repeat 1 (HR1) and heptad repeat 2 (HR2). The HR1 region of S2 subunit forms a homotrimeric assembly and exposes three grooves on the surface which are highly conserved and hydrophobic. Thus, it fuses with HR2 through these grooves. This fusion results in six helix bundle formation (6-HB) and brings the host and viral membrane into close contact for virus entry [30]. Therefor this S protein is an important target protein for drug development to inhibit virus entry into host cell. The RBD of S1 subunit can be used as a target site for both antibodies and vaccine development to prevent from binding of virus with host cell membrane [31]. But this part of CoV is highly mutable and therefor can't be used as an ideal target site for broad spectrum antiviral drug development [31]. In contrast to this the HR region of S2 subunit is highly conserved among HCoV and mediates the binding of virus and host membrane by forming 6-HB. Previous studies show that peptides from HR2 region binds with HR1 region and inhibit viral infection. These peptides can be used to inhibit 6-HB formation and prevent from fusion of host and viral membranes. Such peptide is OC43-HR2P which has a broad-spectrum activity. A modified form of OC43-HR2P is EK1 which has more promising results. In Vivo studies show that when EK1 is administered through nasal route then it has more protective effect [32]. Arbitol Arbitol is a broad-spectrum antiviral drug that has been used for influenza

Antibiotic medications
Teicoplanin is a glycopeptide antibiotic which has been used for the bacterial infections caused by Gram positive bacteria such as, streptococcus and staphylococcus bacteria [40]. This antibiotic has also found to be effective against n-CoV. The entry of virus into host cell requires binding of host cell membrane with viral membrane and for that sequential cleavage of S protein of corona virus with TMPRSS2 and cathepsin L is required [41]. The virus first binds with the host cell through its S protein by binding with ACE2 which is present on the surface of cell. Binding of S protein with ACE2 cause conformational change in S protein and cause activation of TMPRSS1 [40, 42] then through process of endocytosis the virus enters early cell endosome and further cleaves by cathepsin L in late endosome [41]. This teicoplanin has found to have potential to prevent from n-CoV to inhibit the enzymatic activity of cathepsin L that is required for S protein activation for viral entry [43].

Conclusion
Current research review based on diagnosis and therapeutics use to treat COVID-19 disease. For diagnosis purpose, RT-qPCR and CT scan are best suitable techniques, however there is no specific antiviral treatment available for this pandemic disease and clinical trials are going on in different regions of the world. Therefor looking towards the current scenario, the best, we can do is to protect yourself from exposure to this virus by following the safety measures given by WHO 2020.