The novel coronavirus 2019-nCoV has become a bane to mankind and spread worldwide and infected many people. Thus, there is an urgent need of a cure for the severe pneumonia disease caused by this virus. In this study, In silico comparative analysis has been done for HIV protease inhibitors on coronavirus 3CLpro protein which has shown the major interactions and common amino acid residues involved in interactions. The amino acid interaction analysis has revealed two amino acids ARG4, LYS5 to be the major amino acids targets among selected ligands. The binding energy analysis has also revealed Cobicistat as one of these best suited ligand for 3CLpro.
COVID-19 virus structural components: The 2019-nCoV, also called SARS-CoV-2, was first reported in Wuhan, China in December 2019. The disease was named Coronavirus Disease 2019 (COVID-19) and the virus responsible for it as the COVID-19 virus, respectively, by WHO. The 2019-nCoV has a round, elliptic or pleomorphic form with a diameter of 60–140 nm. It has single-stranded RNA genome containing 29891 nucleotides, a lipid shell, and spike, envelope, membrane and hemagglutinin-esterase (HE) proteins.
Steps in progression of COVID-19 illness: Once inside the airways, the S protein on the viral surface recognizes and mediates the attachment to host ACE-2 receptors and gains access to endoplasmic reticulum. The HE protein facilitates the S protein-mediated cell entry and virus spread through the mucosa, helping the virus to attack the ACE2-bearing cells lining the airways and infecting upper as well as lower respiratory tracts. With the dying cells sloughing down and filling the airways, the virus is carried deeper into the lungs. In addition, the virus is able to infect ACE2-bearing cells in other organs, including the blood vessels, gut and kidneys. With the viral infestation, the activated immune system leads to inflammation, pyrexia and pulmonary edema. The hyperactivated immune response, called cytokine storm in extreme cases, can damage various organs apart from lungs and increases susceptibility to infectious bacteria especially in those suffering from chronic diseases.
The current therapeutics for COVID-19: At present, there is no specific antiviral treatment available for the disease. The milder cases may need no treatment. In moderate to severe cases, the clinical management includes infection prevention and control measures, and symptomatic and supportive care, including supplementary oxygen therapy. In the critically ill patients, mechanical ventilation is required for respiratory failure and hemodynamic support is imperative for managing circulatory failure and septic shock.
Conclusion: Confusion, despair and hopes: There is no vaccine for preexposure prophylaxis or postexposure management. There are no specific approved drugs for the treatment for the disease. A number of drugs approved for other conditions as well as several investigational drugs are being canned and studied in several clinical trials for their likely role in COVID-19 prophylaxis or treatment. The future seems afflicted with dormant therapeutic options as well as faux Espoir or false hopes. As obvious, not all clinical trials will be successful, but having so many efforts in progress, some may succeed and provide a positive solution. Right now, though, confusion and despair prevail.
The new coronavirus SARS-CoV-2 that causes different infections in humans has become a challenge for humanity because it has caused many deaths worldwide. This new virus is considered as a zoonotic infectious particle, the clear mechanisms of the pathogenicity and transmissibility of this virus are not exactly known. Therefore, here some characteristics of a possible transmission are analyzed for house flies.
Zinc induced pediatric preventing respiratory 2019-nCoV is required that supplementation with zinc gluconate 20 mg in Zn deficient children resulted in a nearly twofold reduction of acute lower respiratory infections as well as the time to recovery. Zinc supplementation in children is associated with a reduction in the incidence and prevalence of pneumonia. Preventing 2019-nCoV pneumonia is required that zinc supplementation alone (10 to 20 mg) for more than 3 months significantly reduces in the rate of pneumonia. zinc pediatric intake may be required to be effective range 10～20 mg/d for 2019-CoV prevention, 10～30 mg/d for reduction of COVID-19 bronchitis, and 20～30 mg/d for recovery from COVID-19 pneumonia, in which Zn2+ could bind with viral surface proteins by Zn2+ions-centered tetrahedrally coordination pattern.
On the other hand, for aults, the zinc-homeostatic immune concentration may provide a protective role against the COVID-19 pandemic, likely by improving the host’s resistance against viral infection. 50 mg of zinc per day might provide an additional shield against the COVID-19 pandemic, possibly by increasing the host resistance to viral infection to minimize the burden of the disease. In order to prevent that an outbreak of respiratory sickness caused by a novel coronavirus (COVID-19) has become a serious public threat and disrupted many lives,assessing the efficacy of FDA-approved Zn-ejector drugs such as disulfiram combined with interferon to treat COVID-19 infected patients has been proposed. The key strategies for preventing lung damages include avoiding direct lung infection, altering host-virus interactions, promoting immune responses, diluting virus concentrations in lung tissues by promoting viral migration to the rest of the body, maintaining waste removal balance, protecting heart function and renal function, avoiding other infections, reducing allergic reactions and anti-inflammatory. The interactions had been found on the binding specificity by Zn2+ ions-centered tetrahedral geometric coordination of the inhibitors against 3C and 3C-like proteases. In addition, transient zinc chelation TPEN and EPDTC have been noted as preventing virus replication.
Zinc-induced ROS production in COVID-19 respiratory ailment and pneumonia occurs both in children and adults. In children.
ROS production in zinc (Ⅱ)-immune pediatric patient with COVID-19 bronchitis and pneumonia cannot be elucidated yet. In adults, zinc induced ROS generation in pulmonary COVID-19 infected cells is that alterations of ROS-producing and scavenging pathways that are caused by respiratory viral infections are implicated in inﬂammation, lung epithelial disruption, and tissue damage, and, in some cases, even pulmonary ﬁbrosis. The involvement of oxidative stress in cell deaths caused during RNA virus infection and ROS production is correlated with host cell death.
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