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1.
J Biomol Struct Dyn ; : 1-12, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37811765

RESUMO

Radiation resistance is one of the major problems in the treatment of small cell lung cancer (SCLC). Most of these patients are given radiation as first-line treatment and it was observed that the initial response in these patients is very good. However, they show relapse in a few months which is also associated with resistance to treatment. Thus, targeting the mechanism by which these cells develop resistance could be an important strategy to improve the survival chances of these patients. From the RNA-Seq data analysis, it was identified that CHEK1 gene was overexpressed. Chk1 protein which is encoded by the CHEK1 gene is an important protein that is involved in radiation resistance in SCLC. It is known to favour the cells to deal with replicative stress. CHEK1 is the major cause for developing radiation resistance in SCLC. Thus, natural compounds that could also serve as potential inhibitors for Chk1 were explored. Accordingly; the compounds were screened based on ADME, docking and MM-GBSA scores. MD simulations were performed for the selected protein-ligand complexes and the results were compared to the co-crystallised ligand, 3-(indol-2-yl)indazole. The results showed that compound INC000033832986 could be a natural alternative to the commercial ligand for the prevention of SCLC.Communicated by Ramaswamy H. Sarma.

2.
J Biomol Struct Dyn ; 41(1): 16-25, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-34791969

RESUMO

Cancer care has become a challenge with the current COVID-19 pandemic scenario. Specially, cancers like small cell lung cancers (SCLC) are difficult to treat even in the normal situation due to their rapid growth and early metastasis. For such patients, treatment can't be compromised and care must be taken to ensure their minimum exposure to the ongoing spread of COVID-19 infection. For this reason, in-house treatments are being suggested for these patients. Another issue is that symptoms of SCLC match well with that of COVID-19 infection. Hence, the detection of COVID-19 may also get delayed leading to unnecessary complications. Thus, we have tried to investigate if the therapeutics that is currently used in lung cancer treatment can also act against SARS-CoV-2. If it is so, the same treatment protocols can be continued even if the SCLC patient had contracted COVID-19 without compromising the cancer care. For this, RNA dependent RNA polymerase (RdRP) from SARS-CoV-2 has been selected as drug target. Both docking and molecular dynamicssimulation analysis have indicated that Paclitaxel and Dacomitinib may be explored as multi-target drugs for both SCLC and COVID-19.Communicated by Ramaswamy H. Sarma.


Assuntos
COVID-19 , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Simulação de Dinâmica Molecular , Reposicionamento de Medicamentos , Pandemias , SARS-CoV-2 , Neoplasias Pulmonares/tratamento farmacológico , Simulação de Acoplamento Molecular , Antivirais
3.
Biomed Mater ; 17(2)2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35105823

RESUMO

Nearly 80% of human chronic infections are caused due to bacterial biofilm formation. This is the most leading cause for failure of medical implants resulting in high morbidity and mortality. In addition, biofilms are also known to cause serious problems in food industry. Biofilm impart enhanced antibiotic resistance and become recalcitrant to host immune responses leading to persistent and recurrent infections. It makes the clinical treatment for biofilm infections very difficult. Reduced penetration of antibiotic molecules through EPS, mutation of the target site, accumulation of antibiotic degrading enzymes, enhanced expression of efflux pump genes are the probable causes for antibiotics resistance. Accordingly, strategies like administration of topical antibiotics and combined therapy of antibiotics with antimicrobial peptides are considered for alternate options to overcome the antibiotics resistance. A number of other remediation strategies for both biofilm inhibition and dispersion of established biofilm have been developed. The metallic nanoparticles (NPs) and their oxides have recently gained a tremendous thrust as antibiofilm therapy for their unique features. This present comprehensive review gives the understanding of antibiotic resistance mechanisms of biofilm and provides an overview of various currently available biofilm remediation strategies, focusing primarily on the applications of metallic NPs and their oxides.


Assuntos
Infecções Bacterianas , Biofilmes , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Resistência Microbiana a Medicamentos , Humanos
4.
Front Biosci (Landmark Ed) ; 26(6): 149-170, 2021 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-34162043

RESUMO

The disease COVID-19 caused by SARS-CoV-2 is the third highly infectious human Coronavirus epidemic in the 21s⁢t century due to its high transmission rate and quick evolution of its pathogenicity. Genomic studies indicate that it is zoonotic from bats. The COVID-19 has led to significant loss of lives and a tremendous economic decline in the world. Generally, the population at risk of a fatal outcome are the elderly and those who are debilitated or are immune compromised. The fatality rate is high, but now is reduced after the development of preventive vaccine although an effective treatment by drug against the virus is yet to be developed. The treatment is narrowed to the use of several anti-viral drugs, or other re-purposed drugs. Social distancing, therefore, has emerged as a putative method to decrease the rate of infection. In this review, we summarize the aspects of the disease that is so far have come to light and review the impact of the infection on our society, healthcare, economy, education, and environment.


Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Vacinas contra COVID-19/administração & dosagem , Controle de Doenças Transmissíveis/métodos , SARS-CoV-2/efeitos dos fármacos , COVID-19/epidemiologia , COVID-19/virologia , Vacinas contra COVID-19/imunologia , Surtos de Doenças/prevenção & controle , Desinfecção das Mãos/métodos , Humanos , Distanciamento Físico , Saúde Pública/economia , Saúde Pública/métodos , SARS-CoV-2/imunologia , SARS-CoV-2/fisiologia
5.
Adv Exp Med Biol ; 1353: 23-45, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35137366

RESUMO

INTRODUCTION: After the outbreak from Wuhan City of China, COVID-19, caused by SARS-CoV-2, has become a pandemic worldwide in a very short span of time. The high transmission rate and pathogenicity of this virus have made COVID-19 a major public health concern globally. Basically, the emergence of SARS-CoV-2 is the third introduction of a highly infectious human epidemic coronavirus in the twenty-first century. Various research groups have claimed bats to be the natural host of SARS-CoV-2. However, the intermediate host and mode of transmission from bat to humans are not revealed yet. The COVID-19 cost hundreds and thousands of lives and millions are facing the consequences. The objective of this chapter was to analyze the outbreak of COVID-19 and problems faced globally. METHODS: All published relevant literature from scientific sources and reputed news channels are considered to write the current review. RESULTS: Generally, elder persons and more particularly people with underlying medical conditions are found to be highly vulnerable to severe infection and prone to fatal outcomes. Unfortunately, there is no specific treatment with clinically approved drugs or vaccines to treat this disease. Several research groups have been investigating the efficacies of several antiviral and repurposed drugs. Currently, most of the SARS-COV-2 vaccines are at the preclinical or clinical stage of development. The latest research progress on the epidemiology, clinical characteristics, pathogenesis, diagnosis, and current status of therapeutic intervention indicates that still a specific drug or vaccine needs to come up for the effective treatment of the pandemic COVID-19. It is observed that various aspects of social life, economic status, and healthcare systems are majorly affected by this pandemic. CONCLUSION: It is concluded that the outbreak of COVID-19 has severely affected each and every field, such as social, scientific, industrial, transport, and medical sectors. Irrespective of tremendous efforts globally, few vaccines are now available for the prevention of the disease. Specific drug is not available publicly for the treatment of COVID-19. Prevention of air pollution that can aggravate COVID-19 has been suggested. Therefore, as of now, social distancing and sanitization practices are the only options available for the prevention of the disease for many.


Assuntos
COVID-19 , Idoso , Vacinas contra COVID-19 , Surtos de Doenças , Humanos , Pandemias , SARS-CoV-2
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