Computational studies suggest compounds restoring function of p53 cancer mutants can bind SARS-CoV-2 spike protein.

It is reasonable to think that cancer patients undergoing chemotherapy or immunotherapy may have a more aggressive course if they are positive for the novel coronavirus disease. Their compulsive condition requires investigation into effective drugs. We applied computational techniques to a series of compounds known for restoring the function of p53 cancer mutant p53R175H and p53G245S. Two potent inhibitors, 1-(3-chlorophenyl)-3-(1, 3 -thiazol-2-yl) urea (CTU, PubChem NSC321792) with the highest binding affinity -6.92 kcal/mol followed by a thiosemicarbazone compound N'-(1-(Pyridin-2-yl)ethylidene) azetidine - 1 -carbothiohydrazide (NPC, PubChem NSC319726) with -6.75 kcal/mol were subjected to Molecular Dynamics simulation with receptor binding domain (RBD) and compared with control ligand dexamethasone. In particular, CTU adheres to pocket 1 with an average free energy of binding -21.65 ± 2.89 kcal/mol at the RBD - angiotensin-converting enzyme 2 binding region with the highest frequency of amino acid residues after reaching a local equilibrium in 100 ns MD simulation trajectory. A significant enthalpy contribution from the independent simulations unfolds the possibility of dual binding sites for NPC as shifted pocket 1 (-15.59 ± 5.98 kcal/mol) and pocket 2 (-18.90 ± 5.02 kcal/mol). The obtained results for these two compounds are in good agreement with dexamethasone (-18.45 ± 2.42 kcal/mol). Taken together our findings could facilitate the discovery of small molecules that restore the function of p53 cancer mutants newly against COVID-19 in cancer patients.

Identification of possible binding modes of SARS-CoV-2 spike N-terminal domain for ganglioside GM1.

Coarse-grained molecular dynamics simulations of the lipid bilayer mixture of POPC and cholesterol were carried out in the presence and absence of ganglioside monosialo 1 (GM1) with N - terminal domain (NTD) of SARS-CoV-2 spike glycoprotein. The interactions of GM1 with two different NTD orientations were compared. NTD orientation I compactly bind GM1 predominantly through the sialic acid and the external galactose moieties providing more restriction to GM1 mobility whereas orientation II is more distributed on the lipid surface and due to the relaxed mobility of GM1 there, presumably, the NTD receptor penetrates more through the membrane.

Intersectional tension: a qualitative study of the effects of the COVID-19 response on survivors of violence against women in urban India.

OBJECTIVES: There is a concern worldwide that efforts to address the SARS-CoV-2 pandemic have affected the frequency and intensity of domestic violence against women. Residents of urban informal settlements faced particularly stringent conditions during the response in India. Counsellors spoke with registered survivors of domestic violence in Mumbai, with two objectives: to understand how the pandemic and subsequent lockdown had changed their needs and experiences, and to recommend programmatic responses. DESIGN: Qualitative interviews and framework analysis. SETTING: A non-government support programme for survivors of violence against women, providing services mainly for residents of informal settlements. PARTICIPANTS: During follow-up telephone counselling with survivors of violence against women who had previously registered for support and consented to the use of information in research, counsellors took verbal consent for additional questions about the effects of COVID-19 on their daily life, their ability to speak with someone, and their counselling preferences. Responses were recorded as written notes. RESULTS: The major concerns of 586 clients interviewed between April and July 2020 were meeting basic needs (financial stress, interrupted livelihoods and food insecurity), confinement in small homes (family tensions and isolation with abusers) and limited mobility (power imbalances in the home and lack of opportunity for disclosure and stress relief). A major source of stress was the increased burden of unpaid domestic care, which fell largely on women. CONCLUSION: The COVID-19 pandemic has increased the burden of poverty and gendered unpaid care. Finance and food security are critical considerations for future response, which should consider inequality, financial support, prioritising continued availability of services for survivors of violence and expanding access to social networks. Decision-makers must be aware of the gendered, intersectional effects of interventions and must include residents of informal settlements who are survivors of domestic violence in the planning and implementation of public health strategies.