Investigating the novel acetonitrile derivatives as potential SARS-CoV-2 main protease inhibitor using molecular modeling approach.

The COVID-19 is declared a pandemic by World Health Organization (WHO). It causes respiratory illness which leads to oxygen deficiency; it has affected millions of lives all around the globe. It has also been observed that people with diabetes condition are more likely to have severe symptoms when infected with the SARS-CoV2. So, continued efforts are being taken to design and discover potential anti-covid drugs. Earlier, a study reveals that the acetonitrile (2-phenyl-4H-benzopyrimedo [2,1-b]-thiazol-4-yliden) derivatives have potential anti-diabetic activity. Hence, drugs repurpose approach was used to identify the potential acetonitrile derivative targeting the main protease of SARS-CoV2. Here, ADMET, molecular docking, and molecular dynamics simulation techniques were employed, to identify potential acetonitrile compounds against the main protease. The acetonitrile compounds (A to M) show the drug-likeness properties. Next, the molecular docking and dynamics simulation study reveals that acetonitrile compounds A, F, G, and L show a higher binding affinity and have an effect on the structure and dynamics of the main protease. Furthermore, binding energy calculations reveal that the acetonitrile derivative F has a higher binding affinity with the main protease and derivative L has a lower binding affinity with the main protease. The binding affinity of acetonitrile derivatives decreases in the order of F > A > G > L with the main protease. Thus, our computational modeling study provides valuable structural and energetic information of interaction of potential acetonitrile derivatives with the main protease which could be further used as potential lead molecules against the SARS-CoV2.Communicated by Ramaswamy H. Sarma.

COVID-19 in cancer patients on active systemic therapy - Outcomes from LMIC scenario with an emphasis on need for active treatment.

BACKGROUND: There is limited data on outcomes in cancer patients with coronavirus disease 2019 (COVID-19) from lower middle-income countries (LMICs). PATIENTS AND METHODS: This was an observational study, conducted between 12 April and 10 June 2020 at Tata Memorial centre, Mumbai, in cancer patients undergoing systemic therapy with laboratory confirmed COVID-19. The objectives were to evaluate cumulative 30-day all-cause mortality, COVID-19 attributable mortality, factors predicting mortality, and time to viral negativity after initial diagnosis. RESULTS: Of the 24 660 footfalls and 7043 patients evaluated, 230 patients on active systemic therapy with a median age of 42 (1-75) years were included. COVID-19 infection severity, as per WHO criteria, was mild, moderate, and severe in 195 (85%), 11 (5%), and 24 (11%) patients, respectively. Twenty-three patients (10%) expired during follow-up, with COVID-19 attributable mortality seen in 15 patients (6.5%). There were no mortalities in the pediatric cohort of 31 (14%) patients. Advanced stage cancer being treated with palliative intent vs others [30-day mortality 24%% vs 5%, odds ratio (OR) 5.6, 95% CI 2.28-13.78, P < .001], uncontrolled cancer status vs controlled cancer (30-day mortality37.5%% vs 4%%, OR 14, 95% CI 4.46-44.16, P < .001) and severe COVID-19 vs mild COVID-19 (30-day mortality 71% vs 3%, OR 92.29, 95% CI 26.43-322.21, P < .001) were significantly associated with mortality. The median time to SARS-CoV-2 RT-PCR negativity was 17 days [interquartile range (IQR)17-28) in the cohort. CONCLUSIONS: The mortality rates in cancer patients with COVID-19 who are receiving systemic anti-cancer therapy in LMICSs are marginally higher than that reported in unselected COVID-19 cohorts with prolonged time to viral negativity in a substantial number of patients. The pediatric cancer patients tended to have favorable outcomes.

The effects of COVID-19 on perioperative morbidity and mortality in patients with hip fractures.

AIMS: During the COVID-19 pandemic, many patients continue to require urgent surgery for hip fractures. However, the impact of COVID-19 on perioperative outcomes in these high-risk patients remains unknown. The objectives of this study were to establish the effects of COVID-19 on perioperative morbidity and mortality, and determine any risk factors for increased mortality in patients with COVID-19 undergoing hip fracture surgery. METHODS: This multicentre cohort study included 340 COVID-19-negative patients versus 82 COVID-19-positive patients undergoing surgical treatment for hip fractures across nine NHS hospitals in Greater London, UK. Patients in both treatment groups were comparable for age, sex, body mass index, fracture configuration, and type of surgery performed. Predefined perioperative outcomes were recorded within a 30-day postoperative period. Univariate and multivariate analysis were used to identify risk factors associated with increased risk of mortality. RESULTS: COVID-19-positive patients had increased postoperative mortality rates (30.5% (25/82) vs 10.3% (35/340) respectively, p < 0.001) compared to COVID-19-negative patients. Risk factors for increased mortality in patients with COVID-19 undergoing surgery included positive smoking status (hazard ratio (HR) 15.4 (95% confidence interval (CI) 4.55 to 52.2; p < 0.001) and greater than three comorbidities (HR 13.5 (95% CI 2.82 to 66.0, p < 0.001). COVID-19-positive patients had increased risk of postoperative complications (89.0% (73/82) vs 35.0% (119/340) respectively; p < 0.001), more critical care unit admissions (61.0% (50/82) vs 18.2% (62/340) respectively; p < 0.001), and increased length of hospital stay (mean 13.8 days (SD 4.6) vs 6.7 days (SD 2.5) respectively; p < 0.001), compared to COVID-19-negative patients. CONCLUSION: Hip fracture surgery in COVID-19-positive patients was associated with increased length of hospital stay, more admissions to the critical care unit, higher risk of perioperative complications, and increased mortality rates compared to COVID-19-negative patients. Risk factors for increased mortality in patients with COVID-19 undergoing surgery included positive smoking status and multiple (greater than three) comorbidities. Cite this article: Bone Joint J 2020;102-B(9):1136-1145.

Should we wait or not? The preferable option for patients with stage IV oral cancer in COVID-19 pandemic.

BACKGROUND: The coronavirus infection is rapidly spreading, putting a strain on health care services across the globe. Patients with oral cancer are susceptible often immunosuppressed due to the disease and/or the treatment received. METHODS: We performed a simulation of the currently available data using a multistate and hazards model to provide an objective model for counseling and decision making for health care workers. RESULTS: Stage IV patients with oral cancer who did not receive treatment had progression of disease and an increased mortality rate compared to patients who receive treatment but did not contract COVID-19. The patients who received treatment and got affected with COVID-19 had a far worse impact and higher mortality rate than all other groups. CONCLUSION: Isolation and deferring treatment for stage IV patients with oral cancer, so as to avoid hospital visits and contraction of COVID-19, is an advisable strategy based on this model.

Tackling brain metastases from lung cancer during the COVID-19 pandemic

Abstract Given the enormous strain the COVID-19 pandemic has put on healthcare worldwide, appropriate allocation of resources according to priority is of immense importance. As brain metastases are a common presentation in lung cancer, during the pandemic, it potentially can pose a major management challenge to clinicians. In this article, we outline a pragmatic approach that oncologists should consider while managing these patients. The overarching principle is to deliver best, evidence-based treatment without compromising patient care while ensuring the safety of healthcare workers.