In post-mortem, the lungs show consolidation in different degrees. Serum, fibrinous exudate, and transparent membrane formation are seen in the alveolar cavity; exudation cells are mainly monocytes and macrophages, and multinucleated giant cells are easily seen. Type 2 alveolar epithelial cells are proliferated significantly, and some of the cells shed. Inclusion bodies can be seen in type 2 alveolar epithelial cells and macrophages. Alveolar septal vascular congestion and edema, monocyte and lymphocyte infiltration, and intravascular thrombosis can be seen.
A series of cases of pneunomia of unknown cause was reported in Wuhan, in late December 2019. Epidemiological data demonstrated person-to-person spread is the main mode of transmission, which resulted in a worldwide outbreak. World Health Organization (WHO) designated COVID-19 as the official name. The pathogen was confirmed to be severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a betacoronavirus. Standard technique to confirm COVID-19 is nucleic acid testing with reverse transcription polymerase chain reaction (RT-PCR) and/or next-gen sequencing (NGS) methods. Imaging features differ in different individuals and stages of the COVID-19 penumonia, and they are also different from other infectious pulmonary diseases.
Other most important research on plasma therapy is ongoing. Several convalescent patients are donating plasma against COVID-19 based on the positive results of another coronavirus. Surprisingly, it has preliminarily obtained favourable results in severe COVID-19 patients. On the other hand, the recombinant human monoclonal antibody is a straightforward path to neutralize viral load of COVID-19. CR3022 is a coronavirus-specific human monoclonal antibody that can bind to the receptor-binding domain of COVID-19, this has the potential to be developed as candidate therapeutics of COVID-19 disease. Other monoclonal, m396, CR3014 antibodies, neutralizing COVID-19 that may be an alternative for treatment of more severe cases.
Azithromycin has been displayed an antiviral property against zika and ebola virus in vitro. It can prevent severe respiratory tract infection in the case of viral infected patients. Gautret group have treated successfully chronic disease patients with long-term hydroxychloroquine medicines with 600 mg per day for 12 to 18 months. As 17 march 2020, a paper reported (Gautret et al., 2020), they are monitored the viral load in the COVID-19 patients with and without receiving drugs for the six days. They have examined a total of 36 patients, 20 hydroxychloroquine-treated patients and 16 control patients. Among hydroxychloroquine-treated patients, six patients received azithromycin with 500 mg on day 1 followed by 250 mg per day for the next four days. At day 6, 100% patients treated with hydroxychloroquine and azithromycin combination have cured comparing with 57% in patients treated with hydroxychloroquin only, and 12,5% in the control group. Finally they found that hydroxychloroquine and azithromycin combination have cured the COVID-19 patients but the drawback of this study is used a very small size of survey.
Cao et al. have conducted trial test using lopinavir-ritonavir drugs for COVID-19 patients. They found that lopinavir-ritonavir treatment failed to significantly accelerate clinical improvement, reduce mortality, diminish throat viral RNA detectability in patients with serious COVID-19. In case of the severe COVID-19 adult patients, no benefit was observed with lopinavir-ritonavir treatment in comparison to the standard care group. Such study has found that lopinavir-ritonavir does not seem to be effective for COVID-19 patients and these combinations has produced more side effects.
The hydroxychloroquin has shown a potent efficacy in treating patients with COVID-19 pneumonia. More than hundred patients showed the superiority of chloroquine compared with treatment of standard care in terms of reduction of exacerbation of pneumonia, viral load and symptoms. Colson group have suggested that chloroquine and hydroxychloroquine as available weapons to fight COVID-19.
In a short time, the response of the scientific community is such that involve enormous efforts to develop a novel therapy and treatment. For example, chloroquine and hydroxychloroquine, old drugs, have been used to treat malarial, rheumatoid arthritis, lupus and sun allergies for more than sixty years. The activity of hydroxychloroquine on viruses is probably same as that of chloroquine since the mechanism of the action of these two molecules is identical. Chloroquine as an antimalarial and autoimmune disease drugs shown a synergically enhancing effect as antiviral drugs in vivo studies. It interferes with terminal glycosylation of cellular receptor, angiotensin-converting enzyme 2. This may negatively influence-receptor binding and abrogate the infection, with further ramifications by the elevation of vesicular pH, resulting the spread of SARSCoV in cell culture has been prevented.
Trial test of the FDA-approved drugs for COVID-19 patients
Nowdays, the drug repurposing has been used to identify potential drugs against coronavirus. Enormous efforts have been paid for the ability to reuse FDA approved/preclinical trial drugs for the disease. The WHO has provided the permission to doctor and scientist carry out the trial test with the combination of different FDA-approved drugs for COVID-19 treatment. In the view of urgency and current need, to reduce the cost, time and risks of the drug development process, scientists are involved in reusing already approved drug candidates to test in COVID-19 patients
Further, it can form several hydrogen bonds with the main chain of the residues in the substrate-binding pocket. Several X-ray studies demonstrated that the small antiviral compound including lopinar is locked in the same position of N3 in the substrate-binding pocket. The second region of the COVID-19 main protease is the favorable position for the inhibitors binding.
Recently, Jin et al., have constructed a homology model for COVID-19 main protein and they used molecular docking to monitor whether the N3 binds with it. The docking showed that N3 binds with the COVID-19 main protease. Subsequently, the crystal structure of COVID-19 main protease in complex with N3 inhibitor have been determined at 2.3A resolution and deposited in the protein data bank, where the N3 inhibitor binds with the residues of 164-168 in the long strand 155-168 residues, and with residues 189-191 of the loop connecting between second and third region.