Selected Phytochemicals to Combat Lungs Injury: Natural Care.

The human has two lungs responsible for respiration and drug metabolism. Severe lung infection caused by bacteria, mycobacteria, viruses, fungi, and parasites may lead to lungs injury. Smoking and tobacco consumption may also produce lungs injury. Inflammatory and pain mediators are secreted by alveolar macrophages. The inflammatory mediators, such as cytokines, interleukin (IL)-1, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α, neutrophils, and fibroblasts are accumulated in the alveoli sac, which becomes infected. It may lead to hypoxia followed by severe pulmonary congestion and the death of the patient. There is an urgent need for the treatment of artificial respiration and ventilation. However, the situation may be the worst for patients suffering from lung cancer, pulmonary tuberculosis, and acute pneumonia caused by acute respiratory distress syndrome (ARDS). Re-urgency has been happening in the case of coronavirus disease of 2019 (COVID-19) patients. Therefore, it is needed to protect the lungs with the intake of natural phytomedicines. In the present review, several selected phyto components having the potential role in lung injury therapy have been discussed. Regular intake of natural vegetables and fruits bearing these constituents may save the lungs even in the dangerous attack of SARS-CoV-2 in lung cancer, pulmonary TB, and pneumatic patients.

Repurposing of chemotherapeutics to combat COVID-19.

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a novel strain of SARS coronavirus. The COVID-19 disease caused by this virus was declared a pandemic by the World Health Organization (WHO). SARS-CoV-2 mainly spreads through droplets sprayed by coughs or sneezes of the infected to a healthy person within the vicinity of 6 feet. It also spreads through asymptomatic carriers and has negative impact on the global economy, security and lives of people since 2019. Numerous lives have been lost to this viral infection; hence there is an emergency to build up a potent measure to combat SARS-CoV-2. In view of the non-availability of any drugs or vaccines at the time of its eruption, the existing antivirals, antibacterials, antimalarials, mucolytic agents and antipyretic paracetamol were used to treat the COVID-19 patients. Still there are no specific small molecule chemotherapeutics available to combat COVID-19 except for a few vaccines approved for emergency use only. Thus, the repurposing of chemotherapeutics with the potential to treat COVID-19 infected people is being used. The antiviral activity for COVID-19 and biochemical mechanisms of the repurposed drugs are being explored by the biological assay screening and structure-based in silico docking simulations. The present study describes the various US-FDA approved chemotherapeutics repositioned to combat COVID-19 along with their screening for biological activity, pharmacokinetic and pharmacodynamic evaluation.

Exploring the targets of novel corona virus and docking-based screening of potential natural inhibitors to combat COVID-19.

There is a need to explore natural compounds against COVID-19 due to their multi-targeted actions against various targets of nCoV. They act on multiple sites rather than single targets against several diseases. Thus, there is a possibility that the natural resources can be repurposed to combat the COVID-19. However, the biochemical mechanisms of these inhibitors were not known. To reveal the mode of anti-nCoV action, structure-based docking plays a major role. The present study is an attempt to explore various potential targets of SARS-CoV-2 and the structure-based screening of various potential natural inhibitors to combat the novel corona virus.

QSAR of SARS-CoV-2 Main Protease Inhibitors Utilizing Theoretical Molecular Descriptors (preprint)

The COVID-19 caused by novel strain of severe acute respiratory syndrome coronaviruses (SARS-CoV-2), has caused fatalities around the world since the end of 2019 due to its high virulence and quick multiplicity in the human body. Hence there has been an exigency to develop effective remedial measures to mitigate the mortalities. Scientists have been able to develop few corona vaccines to provide immunity, but there are no specific small molecule chemotherapeutics to combat the novel coronavirus which has spread to the whole world due to its contagiousness. In the viral genome exploration, it has been found that the main protease also known as chymotrypsin-like cysteine protease ([M pro ] or 3C-like protease [3CL pro ]) is responsible for the novel corona virus replication, transcription and host immunity destruction. Therefore, the main protease has been selected as one of the major targets for the design of new inhibitors. The protein crystallographic and molecular docking studies on SARS-CoV-2 Mpro inhibitors and some QSAR studies have been carried out on SARS-CoV main protease inhibitors to get some lead molecules for SARS-CoV-2 inhibition. But there is hardly any QSAR done on the diverse data of SARS-CoV-2 main protease inhibitors. In view of it, QSAR studies have been attempted on SARS-CoV-2 M pro inhibitors utilizing theoretical molecular descriptors solely computed from the structures of novel corona viral main protease inhibitors. The developed best QSAR model showing R 2 , Q 2 Loo and R 2 pred values of 0.7389, 0.6666, and 0.6453 respectively has been further validated on external data set where a good correlation (r = 0.787) has been found. Therefore, this model may be useful for the design of new SARS-CoV-2 main protease inhibitors.

Exploring the COVID-19 Potential Targets: Big Challenges to Quest Specific Treatment.

BACKGROUND: The novel strain SARS-CoV-2 of coronavirus diseases (COVID-19) became pandemic at the end of 2019 with an unprecedented global crisis by infecting around 11 million people in more than 200 countries. The condition has now been provoked by the demand, supply, and liquidity shocks that COVID-19 has attacked the lives of a vast population. OBJECTIVES: Researchers are therefore trying to encode and understand the viral genome sequence along with various potential targets to explore the transmission mechanism and the mode of treatment for COVID-19. The important structural proteins such as nucleocapsid protein (N), membrane protein (M), an envelope protein (E), and spike protein (S) related to COVID-19 are discussed in this manuscript. METHODS: The topology of these various targets has been explored utilizing structure-based design and crystallographic studies. RESULTS: The literature reported that the N-protein processes the viral genome to the host cell during replication. The "N-terminal domain" and "C-terminal domain" contribute towards localization in the endoplasmic region and dimerization respectively. The M protein determines the shape of coronavirus and also assists the S protein to integrate with the Golgi-endoplasmic region complex leading to the stabilization of the virion. The smallest hydrophobic viroporin termed "E" takes part in morphogenesis and pathogenesis during intracellular infection. The viral spike (S) protein attaches the cellular receptors and initiates virus-cell membrane fusions. The main protease in the proteolytic process during viral gene expression and replication has also been discussed. CONCLUSION: Currently, there is no permanent cure and treatment of COVID-19 hence researchers are repurposing a suitable combination of drugs including antiviral, antimalarial, antiparasitic, and antibacterial, hypertensive receptor blockers, immunosuppressants, anti-arthritis drugs, including ayurvedic formulations. In brief, it is justified that, for complete recovery, there is a need for deep and elaborate studies on genomic sequences and invading mechanisms in the host cell.

Exploring Spike Protein as Potential Target of Novel Coronavirus and to Inhibit the Viability Utilizing Natural Agents.

BACKGROUND: By the end of 2019, the sudden outbreak of the novel coronavirus disease (COVID-19) has become a global threat. It is called COVID-19 because it was caused by the novel coronavirus (SARS-COV-2) in 2019. A total of 1.9 M deaths and 87.9 M cases have been reported all over the world, where 49M cases have recovered so far. Scientists are working hard to find chemotherapeutics and vaccines for COVID-19. Mutations in SARS-CoV-2 have been observed in a combination of several hazardous stresses, making them more resistant and beneficial. So to break down the viral system, the disease targets are examined. OBJECTIVE: In today's review, a comprehensive study of spike protein explains the main purpose of the novel coronavirus and how to prevent the spread of the disease virus cross-transmission from infected to a healthy person. METHODS: Covid-19 has already been declared a pandemic by the World Health Organization (WHO) due to its result in causing death and severe illness globally. SARS-CoV-2 is highly contagious; however, the intermediate host of the novel coronavirus is not clear. To explore the mechanisms of disease, one of the viral targets, such as the spike protein that binds to human cells and causes the disease by altering its genetic structure which is considered along with potential inhibitors. RESULTS: It has been shown that the interaction of receptor-binding domain (RBD) protein of SARS- CoV-2 spike and the angiotensin-converting enzyme 2 (ACE2) host receptor and further replication of coronavirus spike protein causes its invasion in the host cell. The human Lymphocyte antigen 6 complex, Locus E (LY6E), inhibits the entry of CoV into host cells by interfering with the human gene, inducing spike protein-mediated membrane fusion. Some natural formulations have also been shown to prevent spike protein from binding to the host cell. CONCLUSION: With the development of the LY6E gene activator that can inhibit spike protein- ACE2-mediated membrane fusion, new opportunities for SARS-CoV-2 treatment may emerge. Existing antiviral fusion inhibitors and natural compounds targeting spike resistance can serve as a template for further SARS-CoV-2 drug formulation.

The Antiviral and Antimalarial Drug Repurposing in Quest of Chemotherapeutics to Combat COVID-19 Utilizing Structure-Based Molecular Docking.

BACKGROUND: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) that erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted to the quest of the medicine that can cure COVID-19. OBJECTIVE: Existing antivirals, such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine, have been repurposed to fight the current coronavirus epidemic. Exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. METHODS: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs, including antivirals and antimalarials, to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. RESULTS: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. CONCLUSION: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.