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1.
Curr Pharm Des ; 26(41): 5300-5309, 2020.
Article in English | MEDLINE | ID: covidwho-1073205

ABSTRACT

BACKGROUND: Previously human society has faced various unprecedented pandemics in the history and viruses have majorly held the responsibilities of those outbreaks. Furthermore, due to amplified global connection and speedy modernization, epidemic outbreaks caused by novel and re-emerging viruses signify potential risk to community health. Despite great advancements in immunization and drug discovery processes, various viruses still lack prophylactic vaccines and efficient antiviral therapies. Although, vaccine is a prophylaxes option, but it cannot be applied to infected patients, hence therapeutic interventions are urgently needed to control the ongoing global SARS- CoV-2 pandemic condition. To spot the novel antiviral therapy is of decisive importance and Mother Nature is an excellent source for such discoveries. METHODOLOGY: In this article, prompt high through-put virtual screening for vetting the best possible drug candidates from natural compounds' databases has been implemented. Herein, time tested rigorous multi-layered drug screening process to narrow down 66,969 natural compounds for the identification of potential lead(s) is implemented. Druggability parameters, different docking approaches and neutralization tendency of the natural products were employed in this study to screen the best possible natural compounds from the digital libraries. CONCLUSION: The results of this study conclude that compounds PALA and HMCA are potential inhibitors of SARS-CoV-2 spike protein and can be further explored for experimental validation. Overall, the methodological approach reported in this article can be suitably used to find the potential drug candidates against SARS-CoV2 in the burning situation of COVID-19 with less expenditure and a concise span of time.


Subject(s)
Antiviral Agents , COVID-19 , Antiviral Agents/pharmacology , Humans , Molecular Docking Simulation , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
2.
Life Sci ; 268: 118959, 2021 Mar 01.
Article in English | MEDLINE | ID: covidwho-988728

ABSTRACT

Cystic fibrosis (CF) is an autosomal recessive disease which involves the mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CF involves in the inflammatory processes and is considered as a multisystem disorder that is not confined to lungs, but it also affects other vital organs that leads to numerous co-morbidities. The respiratory disorder in the CF results in mortality and morbidity which is characterized by series of serious events involving mucus hypersecretion, microbial infections, airways obstruction, inflammation, destruction of epithelium, tissue remodeling and terminal lung diseases. Mucins are the high molecular weight glycoproteins important for the viscoelastic properties of the mucus, play a significant role in the disease mechanisms. Determining the functional association between the CFTR and mucins might help to identify the putative target for specific therapeutic approach. In fact, furin enzyme which helps in the entry of novel COVID-19 virus into the cell, is upregulated in CF and this can also serve as a potential target for CF treatment. Moreover, the use of nano-formulations for CF treatment is an area of research being widely studied as they have also demonstrated promising outcomes. The in-depth knowledge of non-coding RNAs like miRNAs and lncRNAs and their functional association with CFTR gene expression and mutation can provide a different range of opportunity to identify the promising therapeutic approaches for CF.


Subject(s)
COVID-19/virology , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis/physiopathology , Animals , Cystic Fibrosis/genetics , Cystic Fibrosis/therapy , Gene Expression Regulation , Humans , MicroRNAs/genetics , Mucins/metabolism , Mutation , RNA, Long Noncoding/genetics , SARS-CoV-2/pathogenicity
3.
Future Drug Discov ; 2(4): FDD50, 2020 Oct 01.
Article in English | MEDLINE | ID: covidwho-955248
4.
Int J Mol Sci ; 21(18)2020 Sep 09.
Article in English | MEDLINE | ID: covidwho-760932

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, an infection caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), has led to more than 771,000 deaths worldwide. Tobacco smoking is a major known risk factor for severe illness and even death from many respiratory infections. The effects of smoking on COVID-19 are currently controversial. Here, we provide an overview of the current knowledge on the effects of smoking on the clinical manifestations, disease progression, inflammatory responses, immunopathogenesis, racial ethnic disparities, and incidence of COVID-19. This review also documents future directions of smoking related research in COVID-19. The current epidemiological finding suggests that active smoking is associated with an increased severity of disease and death in hospitalized COVID-19 patients. Smoking can upregulate the angiotensin-converting enzyme-2 (ACE-2) receptor utilized by SARS-CoV-2 to enter the host cell and activate a 'cytokine storm' which can lead to worsen outcomes in COVID-19 patients. This receptor can also act as a potential therapeutic target for COVID-19 and other infectious diseases. The COVID-19 pandemic sheds light on a legacy of inequalities regarding gender, racial, and ethnic health disparities associated with active smoking, thus, smoking cessation may help in improving outcomes. In addition, to flatten the COVID-19 curve, staying indoors, avoiding unnecessary social contact, and bolstering the immune defense system by maintaining a healthy diet/living are highly desirable.


Subject(s)
Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Smoking/epidemiology , COVID-19 , Humans , Pandemics
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