Impact of COVID-19 pandemic on relapse of individuals with severe mental illness and their caregiver's burden.

Background: The implementation of quarantine and social distancing measures to control the COVID-19 pandemic led to restrictions at the community level and most of in-person psychiatric services were discontinued. This situation could affect the psychopathology of the patients and the burden of their caregivers. The aim of this study was to investigate the effects of COVID-19 pandemic on people with severe mental illnesses (SMIs) and their caregivers' burden. Method: The study sample consisted of 86 patients with severe mental illness and 86 caregivers. The mental status, relapse rate, and rehospitalization rate of the patients and the general health status and burden of caregivers were investigated in three waves, including before and 3 and 6 months after the COVID-19 pandemic. Results: The relapse rate of the patients was 14%, 33.7%, and 43% (p = 0.000) and the rehospitalization rate was 4.7%, 7%, and 10.5% in waves 0, 1, and 2, respectively (p = 0.000). Most of the psychopathological scales increased in three waves (p = 0.000). The caregivers' burden and health condition worsened during the nine months of the study as well (p = 0.000). Conclusion: The COVID-19 pandemic led to the exacerbation of symptoms and increased the relapse rate in people with SMIs. It also worsened the caregivers' condition. People with severe mental illnesses (SMIs) and their caregivers are one of the most vulnerable groups on which the COVID-19 pandemic had a marked negative effect.

Synthetic and computational efforts towards the development of peptidomimetics and small-molecule SARS-CoV 3CLpro inhibitors.

Severe Acute Respiratory Syndrome (SARS) is a severe febrile respiratory disease caused by the beta genus of human coronavirus, known as SARS-CoV. Last year, 2019-n-CoV (COVID-19) was a global threat for everyone caused by the outbreak of SARS-CoV-2. 3CLpro, chymotrypsin-like protease, is a major cysteine protease that substantially contributes throughout the viral life cycle of SARS-CoV and SARS-CoV-2. It is a prospective target for the development of SARS-CoV inhibitors by applying a repurposing strategy. This review focuses on a detailed overview of the chemical synthesis and computational chemistry perspectives of peptidomimetic inhibitors (PIs) and small-molecule inhibitors (SMIs) targeting viral proteinase discovered from 2004 to 2020. The PIs and SMIs are one of the primary therapeutic inventions for SARS-CoV. The journey of different analogues towards the evolution of SARS-CoV 3CLpro inhibitors and complete synthetic preparation of nineteen derivatives of PIs and ten derivatives of SMIs and their computational chemistry perspectives were reviewed. From each class of derivatives, we have identified and highlighted the most compelling PIs and SMIs for SARS-CoV 3CLpro. The protein-ligand interaction of 29 inhibitors were also studied that involved with the 3CLpro inhibition, and the frequent amino acid residues of the protease were also analyzed that are responsible for the interactions with the inhibitors. This work will provide an initiative to encourage further research for the development of effective and drug-like 3CLpro inhibitors against coronaviruses in the near future.

Identification of SARS-CoV-2 Receptor Binding Inhibitors by In Vitro Screening of Drug Libraries.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) global pandemic. The first step of viral infection is cell attachment, which is mediated by the binding of the SARS-CoV-2 receptor binding domain (RBD), part of the virus spike protein, to human angiotensin-converting enzyme 2 (ACE2). Therefore, drug repurposing to discover RBD-ACE2 binding inhibitors may provide a rapid and safe approach for COVID-19 therapy. Here, we describe the development of an in vitro RBD-ACE2 binding assay and its application to identify inhibitors of the interaction of the SARS-CoV-2 RBD to ACE2 by the high-throughput screening of two compound libraries (LOPAC®1280 and DiscoveryProbeTM). Three compounds, heparin sodium, aurintricarboxylic acid (ATA), and ellagic acid, were found to exert an effective binding inhibition, with IC50 values ranging from 0.6 to 5.5 µg/mL. A plaque reduction assay in Vero E6 cells infected with a SARS-CoV-2 surrogate virus confirmed the inhibition efficacy of heparin sodium and ATA. Molecular docking analysis located potential binding sites of these compounds in the RBD. In light of these findings, the screening system described herein can be applied to other drug libraries to discover potent SARS-CoV-2 inhibitors.