ABSTRACT
INTRODUCTION: We aimed to study the prevalence of a history of COVID-19 infection among patients suffering from systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome (SjS) or psoriatic arthritis (PsA), and the potential influence of long-term hydroxychloroquine (HCQ) intake. METHODS: We performed an observational monocentric cohort study at the Adolphe de Rothschild Foundation Hospital ophthalmology division (Paris, France). Electronic medical records (EMR) data were searched for keywords associated with SLE, RA, SjS, or PsA. Patients were contacted by phone and were interviewed using a standardized questionnaire. The primary outcome was the occurrence of a positive COVID-19 test result during the study period. We determined the adjusted association between various antirheumatic drugs intake, COVID-19 risk factors, and occurrence of COVID-19 using a logistic regression model. This study is registered on ClinicalTrials.gov (Identifier: NCT04345159). RESULTS: Patients were recruited between Apr 17, 2020, and Apr 30, 2020 and were recontacted between Oct 6, 2020, and Nov 2, 2020. A total of 569 patients were included, of whom 459 patients were eligible for data analysis. One hundred and eighty-one patients were treated with long-term HCQ and 18 patients had tested positive for COVID-19. No antirheumatic drug intake, including HCQ intake, was significantly associated with an increased or decreased risk of developing COVID-19 infection. CONCLUSIONS: No antirheumatic drug intake was associated with an increased or decreased risk of developing COVID-19 infection in our cohort of patients suffering from immune-mediated inflammatory diseases.
ABSTRACT
The main protease (3CL Mpro) from SARS-CoV-2, the etiological agent of COVID-19, is an essential enzyme for viral replication, possessing an unusual catalytic dyad composed of His41 and Cys145. A long-standing question in the field has been what the protonation states of the ionizable residues in the substrate-binding active site cavity are. Here, we present the room-temperature neutron structure of 3CL Mpro from SARS-CoV-2, which allows direct determination of hydrogen atom positions and, hence, protonation states. The catalytic site natively adopts a zwitterionic reactive state where His41 is doubly protonated and positively charged, and Cys145 is in the negatively charged thiolate state. The neutron structure also identified the protonation states of other amino acid residues, mapping electrical charges and intricate hydrogen bonding networks in the SARS-CoV-2 3CL Mpro active site cavity and dimer interface. This structure highlights the ability of neutron protein crystallography for experimentally determining protonation states at near-physiological temperature -- the critical information for structure-assisted and computational drug design.
Subject(s)
COVID-19ABSTRACT
In a survey of household cats and dogs of laboratory-confirmed COVID-19 patients, we found a high seroprevalence of SARS-CoV-2 antibodies, ranging from 21% to 53%, depending on the positivity criteria chosen. Seropositivity was significantly greater among pets from COVID-19+ households compared to those with owners of unknown status. Our results highlight the potential role of pets in the spread of the epidemic.
Subject(s)
COVID-19ABSTRACT
In recognizing the host cellular receptor and mediating fusion of virus and cell membranes, the spike (S) glycoprotein of coronaviruses is the most critical viral protein for cross-species transmission and infection. Here we determined the cryo-EM structures of the spikes from bat (RaTG13) and pangolin (PCoV_GX) coronaviruses, which are closely related to SARS-CoV-2. All three receptor-binding domains (RBDs) of these two spike trimers are in the "down" conformation, indicating they are more prone to adopt this receptor-binding inactive state. However, we found that the PCoV_GX, but not the RaTG13, spike is comparable to the SARS-CoV-2 spike in binding the human ACE2 receptor and supporting pseudovirus cell entry. Through structure and sequence comparisons, we identified critical residues in the RBD that underlie the different activities of the RaTG13 and PCoV_GX/SARS-CoV-2 spikes and propose that N-linked glycans serve as conformational control elements of the RBD. These results collectively indicate that strong RBD-ACE2 binding and efficient RBD conformational sampling are required for the evolution of SARS-CoV-2 to gain highly efficient infection.