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1.
J Biomol Struct Dyn ; : 1-18, 2021 Aug 25.
Article in English | MEDLINE | ID: covidwho-2257080

ABSTRACT

Severe acute respiratory syndrome coronavirus (SARS-CoV-2), a novel member of the betacoronavirus family is a single-stranded RNA virus that has spread worldwide prompting the World Health Organization to declare a global pandemic. This creates an alarming situation and generates an urgent need to develop innovative therapeutic agents. In this context, an in silico molecular docking and molecular dynamics (MD) simulation study on the existing 58 antiviral and antimalarial compounds was performed on 3CLpro, PLpro and RdRp SARS-CoV-2 proteins. The antiviral compounds are best fitted in the binding pockets and interact more profoundly with the amino acid residues compared to antimalarial compounds. An HIV protease inhibitor, saquinavir showed a good dock score and binding free energy with varied binding interactions against 3CLpro and PLpro. While, adefovir, a nucleotide HBV DNA polymerase inhibitor exhibited good dock score and binding interactions against RdRp. Although, the antimalarial compounds showed relatively less dock score but were found to be crucial in displaying essential binding interactions with these proteins. The MD simulation runs for 100 ns on 3CLpro-saquinavir, PLpro-saquinavir and RdRp-adefovir complexes using Desmond revealed fairly stable nature of interactions. This study helped in understanding the key interactions of the vital functionalities that provide a concrete base to develop lead molecules effective against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

2.
Cancers ; 15(5), 2023.
Article in English | EuropePMC | ID: covidwho-2263632

ABSTRACT

Simple Summary The transurethral resection of bladder tumors followed by intravesical Bacillus Calmette-Guerin (BCG) instillations represents the standard treatment for high-risk and selected intermediate-risk non-muscle invasive bladder cancer (NMIBC) patients. We hypothesized that intravesical BCG might be protective against symptomatic SARS-CoV-2 infection, especially in those patients who experienced systemic adverse events during BCG treatment. We tested our hypothesis in a large multicenter cohort of NMIBC patients treated with adjuvant intravesical BCG in the year preceding the first and second waves of the SARS-CoV-2 pandemic at two tertiary urological centers in Northern Italy. We aim to evaluate the potential protective role of intravesical Bacillus Calmette-Guerin (BCG) against SARS-CoV-2 in patients with non-muscle invasive bladder cancer (NMIBC). Patients treated with intravesical adjuvant therapy for NMIBC between January 2018 and December 2019 at two Italian referral centers were divided into two groups based on the received intravesical treatment regimen (BCG vs. chemotherapy). The study's primary endpoint was evaluating SARS-CoV-2 disease incidence and severity among patients treated with intravesical BCG compared to the control group. The study's secondary endpoint was the evaluation of SARS-CoV-2 infection (estimated with serology testing) in the study groups. Overall, 340 patients treated with BCG and 166 treated with intravesical chemotherapy were included in the study. Among patients treated with BCG, 165 (49%) experienced BCG-related adverse events, and serious adverse events occurred in 33 (10%) patients. Receiving BCG or experiencing systemic BCG-related adverse events were not associated with symptomatic proven SARS-CoV-2 infection (p = 0.9) nor with a positive serology test (p = 0.5). The main limitations are related to the retrospective nature of the study. In this multicenter observational trial, a protective role of intravesical BCG against SARS-CoV-2 could not be demonstrated. These results may be used for decision-making regarding ongoing and future trials.

3.
Cancers (Basel) ; 15(5)2023 Mar 06.
Article in English | MEDLINE | ID: covidwho-2263633

ABSTRACT

We aim to evaluate the potential protective role of intravesical Bacillus Calmette-Guerin (BCG) against SARS-CoV-2 in patients with non-muscle invasive bladder cancer (NMIBC). Patients treated with intravesical adjuvant therapy for NMIBC between January 2018 and December 2019 at two Italian referral centers were divided into two groups based on the received intravesical treatment regimen (BCG vs. chemotherapy). The study's primary endpoint was evaluating SARS-CoV-2 disease incidence and severity among patients treated with intravesical BCG compared to the control group. The study's secondary endpoint was the evaluation of SARS-CoV-2 infection (estimated with serology testing) in the study groups. Overall, 340 patients treated with BCG and 166 treated with intravesical chemotherapy were included in the study. Among patients treated with BCG, 165 (49%) experienced BCG-related adverse events, and serious adverse events occurred in 33 (10%) patients. Receiving BCG or experiencing systemic BCG-related adverse events were not associated with symptomatic proven SARS-CoV-2 infection (p = 0.9) nor with a positive serology test (p = 0.5). The main limitations are related to the retrospective nature of the study. In this multicenter observational trial, a protective role of intravesical BCG against SARS-CoV-2 could not be demonstrated. These results may be used for decision-making regarding ongoing and future trials.

4.
J Biomol Struct Dyn ; : 1-12, 2023 Feb 09.
Article in English | MEDLINE | ID: covidwho-2234246

ABSTRACT

A novel coronavirus SARS-CoV-2 has caused a worldwide pandemic and remained a severe threat to the entire human population. Researchers worldwide are struggling to find an effective drug treatment to combat this deadly disease. Many FDA-approved drugs from varying inhibitory classes and plant-derived compounds are screened to combat this virus. Still, due to the lack of structural information and several mutations of this virus, initial drug discovery efforts have limited success. A high-resolution crystal structure of important proteins like the main protease (3CLpro) that are required for SARS-CoV-2 viral replication and polymerase (RdRp) and papain-like protease (PLpro) as a vital target in other coronaviruses still presents important targets for the drug discovery. With this knowledge, scaffold library of Interbioscreen (IBS) database was explored through molecular docking, MD simulation and postdynamic binding free energy studies. The 3D docking structures and simulation data for the IBS compounds was studied and articulated. The compounds were further evaluated for ADMET studies using QikProp and SwissADME tools. The results revealed that the natural compounds STOCK2N-00385, STOCK2N-00244, and STOCK2N-00331 interacted strongly with 3CLpro, PLpro, and RdRp, respectively, and ADMET data was also observed in the range of limits for almost all the compounds with few exceptions. Thus, it suggests that these compounds may be potential inhibitors of selected target proteins, or their structural scaffolds can be further optimized to obtain effective drug candidates for SARS-CoV-2. The findings of in-silico data need to be supported by in-vivo studies which could shed light on understanding the exact mode of inhibitory action.Communicated by Ramaswamy H. Sarma.

5.
Cureus ; 15(1): e33515, 2023 Jan.
Article in English | MEDLINE | ID: covidwho-2228738

ABSTRACT

Monkeypox virus (MPOX) is a zoonotic disease in humans. It is similar genetically to its virus family member, smallpox. This virus has been studied since the 1970s. The virus remains endemic to the Congo and West African regions, but non-endemic spreads have been cited. The most recent non-endemic outbreak in the spring of 2022 amidst the current COVID-19 pandemic is of interest due to its impact on global medical, economic, and societal climates. This literature review aims to highlight the virology, clinical signs and symptoms, diagnosis, prevention, and treatment of MPOX and discuss the social implications of the recent 2022 outbreak. We hope this review can pinpoint important clinical pearls of the MPOX virus and its societal impacts to further promote important discussion of this virus and its disease.

6.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-2529092.v1

ABSTRACT

COVID-19 caused by novel corona virus (SARS-CoV-2) is the major pandemic of the decade claiming millions of lives causing severe disruptions to society. Despite rapid development of COVID-19 vaccines, condition is still not under control and newer antiviral drugs are required. In the present work, we describe the design and synthesis of Diphenyl-1H-imidazole derivatives as a potential lead series for SARS-CoV-2 3CLpro enzyme inhibition. The synthesized molecules were screened for SARS-CoV-2 3CLpro enzyme inhibition at 20µM concentration. All the synthesized compounds (6-14) showed inhibition in the range of 88 to 99%. They were further tested for anti-SARS-CoV-2 activity against ancestral Wuhan and the Delta variants in virus infected cells. The compounds 4-(4-hlorophenyl)-2-(3,4-dimethoxyphenyl)-1H-imidazole (9), 4-(2,4-dichlorophenyl)-2-(3,4-dimethoxyphenyl)-1H-imidazole (10), 4-(4-(2,4-dichlorophenyl)-1H-imidazol-2-yl)benzene-1,2-diol (14) showed promising activity against both Wuhan (IC50: 7.7 µM, 12.6 µM and 11.8 µM, respectively) and Delta (IC50: 7.4 µM, 13.8 µM and 12.1 µM, respectively) variant of COVID-19.   Our results demonstrate efficacy of diphenyl-1H-imidazole derivatives as promising ligands for further development and optimization against COVID-19.


Subject(s)
COVID-19
7.
Urol Oncol ; 2022 Nov 24.
Article in English | MEDLINE | ID: covidwho-2122869

ABSTRACT

In 1997 an international group of scientists organized a meeting in Barcelona, Spain, to discuss the use of biomarkers in the management of patients with bladder cancer. This meeting was the offspring of an - initially informal - group that finally resulted in the foundation and incorporation of the International Bladder Cancer Network (IBCN) e.V. in 2005. Over the years the group has supported several research initiatives and generated several recommendations on the use of biomarkers in the diagnosis and treatment of bladder cancer. Meeting quality was generated by inviting experts presenting state-of-the-art lectures or work in progress reports, interdisciplinarity and the limited number of participants supporting an open and personal exchange resulted in a format increasingly attracting participants from all over the world. The recent limitations caused by the Covid-19 pandemic were partially met by organizing several well attended webinars. The future challenge is to maintain the IBCN meeting spirit despite an increasing interest of the scientific community and industrial partners to participate. However, the integration of and interaction between increasingly more specialized disciplines is a challenge that can be better catalyzed by an international multidisciplinary network than mostly national professional associations.

8.
3rd International Conference on Intelligent Engineering and Management, ICIEM 2022 ; : 81-88, 2022.
Article in English | Scopus | ID: covidwho-2018835

ABSTRACT

Detection of COVID-19 disease and its unmasking, demands a certain level of proficiency. The Work exhibited in the paper proposes a novel Deep Learning based approach to recognize COVID-19 contagious infection using CT scans and X- Rays of lungs in Humans. So that labour and risk intensive task for radiotherapists of taking samples from the patients can be minimized and risk of community spread can be avoided. Our model takes into the CT scan chest images of the patient having a certainty of infection and returns the most significant disease category related to that patient. In our study, we demonstrated a Deep Learning framework model that follows the methodology of up-skilled feature extraction techniques along with Logistic Regression [LR] and other usable classifiers. This is used on images to detect and report the presence of infection that is being prevailed in an organ with a considerably pinpoint accuracy of 97.8%. Also after trying the model on spatial information real- time dataset of our Family members, who were infected by the disease, this model was able to detect 8 out of 10 images correctly. © 2022 IEEE.

9.
Nat Rev Urol ; 18(10): 611-622, 2021 10.
Article in English | MEDLINE | ID: covidwho-1284696

ABSTRACT

Bacillus Calmette-Guérin (BCG) is the most widely used vaccine worldwide and has been used to prevent tuberculosis for a century. BCG also stimulates an anti-tumour immune response, which urologists have harnessed for the treatment of non-muscle-invasive bladder cancer. A growing body of evidence indicates that BCG offers protection against various non-mycobacterial and viral infections. The non-specific effects of BCG occur via the induction of trained immunity and form the basis for the hypothesis that BCG vaccination could be used to protect against the severity of coronavirus disease 2019 (COVID-19). This Perspective article highlights key milestones in the 100-year history of BCG and projects its potential role in the COVID-19 pandemic.


Subject(s)
Adjuvants, Immunologic/history , BCG Vaccine/history , COVID-19 Vaccines , COVID-19/prevention & control , Immunotherapy/history , Animals , Cattle , History, 19th Century , History, 20th Century , Humans , Infant
10.
Sci Rep ; 11(1): 774, 2021 01 12.
Article in English | MEDLINE | ID: covidwho-1065935

ABSTRACT

Population-level data have suggested that bacille Calmette-Guerin (BCG) vaccination may lessen the severity of Coronavirus Disease-19 (COVID-19) prompting clinical trials in this area. Some reports have demonstrated conflicting results. We performed a robust, ecologic analysis comparing COVID-19 related mortality (CRM) between strictly selected countries based on BCG vaccination program status utilizing publicly available databases and machine learning methods to define the association between active BCG vaccination programs and CRM. Validation was performed using linear regression and country-specific modeling. CRM was lower for the majority of countries with a BCG vaccination policy for at least the preceding 15 years (BCG15). CRM increased significantly for each increase in the percent population over age 65. A higher total population of a country and BCG15 were significantly associated with improved CRM. There was a consistent association between countries with a BCG vaccination for the preceding 15 years, but not other vaccination programs, and CRM. BCG vaccination programs continued to be associated with decreased CRM even for populations < 40 years old where CRM events are less frequent.


Subject(s)
BCG Vaccine/therapeutic use , COVID-19/mortality , Vaccination/statistics & numerical data , COVID-19/epidemiology , Europe , Humans , Republic of Korea , Unsupervised Machine Learning
11.
Mol Divers ; 25(1): 383-401, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-690650

ABSTRACT

The Corona virus Disease (COVID-19) is caused because of novel coronavirus (SARS-CoV-2) pathogen detected in China for the first time, and from there it spread across the globe creating a worldwide pandemic of severe respiratory complications. The virus requires structural and non-structural proteins for its multiplication that are produced from polyproteins obtained by translation of its genomic RNA. These polyproteins are converted into structural and non-structural proteins mainly by the main protease (Mpro). A systematic screening of a drug library (having drugs and diagnostic agents which are approved by FDA or other world authorities) and the Asinex BioDesign library was carried out using pharmacophore and sequential conformational precision level filters using the Schrodinger Suite. From the screening of approved drug library, three antiviral agents ritonavir, nelfinavir and saquinavir were predicted to be the most potent Mpro inhibitors. Apart from these pralmorelin, iodixanol and iotrolan were also identified from the systematic screening. As iodixanol and iotrolan carry some limitations, structural modifications in them could lead to stable and safer antiviral agents. Screenings of Asinex BioDesign library resulted in 20 molecules exhibiting promising interactions with the target protein Mpro. They can broadly be categorized into four classes based on the nature of the scaffold, viz. disubstituted pyrazoles, cyclic amides, pyrrolidine-based compounds and miscellaneous derivatives. These could be used as potential molecules or hits for further drug development to obtain clinically useful therapeutic agents for the treatment of COVID-19.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19 Drug Treatment , Coronavirus 3C Proteases/antagonists & inhibitors , Protease Inhibitors/pharmacology , SARS-CoV-2/drug effects , COVID-19/virology , Drug Evaluation, Preclinical/methods , Humans , Mass Screening/methods , Molecular Docking Simulation , Pandemics/prevention & control , SARS-CoV-2/metabolism , Viral Nonstructural Proteins/antagonists & inhibitors
12.
BJUI Compass ; 1(3): 87-92, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-610522

ABSTRACT

OBJECTIVES: To summarize the available literature regarding bacillus Calmette-Guerin (BCG) administration, severe acute respiratory syndrome conoravirus-2 (SARS-CoV-2), and the resulting clinical condition coronavirus disease (COVID-19) in light of recent epidemiologic work suggesting decreased infection severity in BCG immunized populations while highlighting the potential role of the urologist in clinical trials and ongoing research efforts. MATERIALS AND METHODS: We reviewed the available literature regarding COVID-19 and BCG vaccination. Specifically, the epidemiologic evidence for decreased COVID-19 morbidity in countries with BCG vaccination programs, current clinical trials for BCG vaccination to protect against COVID-19, potential mechanisms and rationale for this protection, and the role of the urologist and urology clinic in providing support and/or leading ongoing efforts. RESULTS: Epidemiologic evidence suggests that the crude case fatality rates are lower for countries with BCG vaccination compared to those without such programs. Four prospective, randomized clinical trials for BCG vaccination were identified including NCT04348370 (BADAS), NCT04327206 (BRACE), NCT04328441 (BCG-CORONA), and NCT04350931. BCG administration may contribute to innate and adaptive immune priming with several opportunities for translational research. CONCLUSIONS: The urologist's expertise with BCG and the infrastructure of urologic clinics may afford several opportunities for collaboration and leadership to evaluate and understand the potential role of BCG in the current COVID-19 pandemic.

13.
researchsquare; 2020.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.pex-976.v1

ABSTRACT

Population-level data have suggested that bacille Calmette-Guerin (BCG) vaccination may lessen the severity of COVID-19; prior reports have demonstrated conflicting results. We leveraged publicly available databases and unsupervised machine learning, adjusting for established confounders designated a priori, to assign countries into similar clusters. The primary outcome was the association of deaths per million related to COVID-19 (CSM) 30 days after each included country reported 100 cases with several factors including vaccination. Validation was performed using linear regression and country-specific modeling. This protocol details the statistical analyses used to establish an association between BCG vaccination and CSM, which includes : Definition of the target function, data processing, exploratory factor analysis for variable selection, k-means clustering and step wise linear regression for validation. This protocol is differentiated from previous works on the same subject by its' comprehensive nature which considers the effect of several confounding variables while studying the association between BCG vaccination and CSM. There are still several potential measured and unmeasured confounding variables which could not be included in this study. It is also unclear if the protection from neonatal vaccination with BCG is transferable to those receiving vaccination as an adult and how long such protection lasts. The authors advise caution against routine BCG vaccination for the prevention of COVID-19 until prospective trials are completed.


Subject(s)
COVID-19
14.
researchsquare; 2020.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-35340.v1

ABSTRACT

Population-level data have suggested that bacille Calmette-Guerin (BCG) vaccination may lessen the severity of Coronavirus Disease-19 (COVID-19) prompting clinical trials in this area. Some reports have demonstrated conflicting results. We performed a robust, ecologic analysis comparing COVID-19 related mortality (CSM) between strictly selected countries based on BCG vaccination program status utilizing publicly available databases and machine learning to define the association between active BCG vaccination programs and CSM. Validation was performed using linear regression and country-specific modeling. CSM was lower for 80% of similarly clustered countries with a BCG vaccination policy for at least the preceding 15 years (BCG15). CSM increased significantly for each increase in the percent population over age 65. The total population of a country and BCG15 were significantly associated with improved CSM. There was a consistent association between countries with a BCG vaccination for the preceding 15 years, but not other vaccination programs, and CSM. 


Subject(s)
COVID-19
16.
Eur Urol Oncol ; 3(3): 259-261, 2020 06.
Article in English | MEDLINE | ID: covidwho-47181
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