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1.
Infect Dis Poverty ; 11(1): 57, 2022 May 22.
Article in English | MEDLINE | ID: covidwho-1902417

ABSTRACT

BACKGROUND: A One Health approach has been increasingly mainstreamed by the international community, as it provides for holistic thinking in recognizing the close links and inter-dependence of the health of humans, animals and the environment. However, the dearth of real-world evidence has hampered application of a One Health approach in shaping policies and practice. This study proposes the development of a potential evaluation tool for One Health performance, in order to contribute to the scientific measurement of One Health approach and the identification of gaps where One Health capacity building is most urgently needed. METHODS: We describe five steps towards a global One Health index (GOHI), including (i) framework formulation; (ii) indicator selection; (iii) database building; (iv) weight determination; and (v) GOHI scores calculation. A cell-like framework for GOHI is proposed, which comprises an external drivers index (EDI), an intrinsic drivers index (IDI) and a core drivers index (CDI). We construct the indicator scheme for GOHI based on this framework after multiple rounds of panel discussions with our expert advisory committee. A fuzzy analytical hierarchy process is adopted to determine the weights for each of the indicators. RESULTS: The weighted indicator scheme of GOHI comprises three first-level indicators, 13 second-level indicators, and 57 third-level indicators. According to the pilot analysis based on the data from more than 200 countries/territories the GOHI scores overall are far from ideal (the highest score of 65.0 out of a maximum score of 100), and we found considerable variations among different countries/territories (31.8-65.0). The results from the pilot analysis are consistent with the results from a literature review, which suggests that a GOHI as a potential tool for the assessment of One Health performance might be feasible. CONCLUSIONS: GOHI-subject to rigorous validation-would represent the world's first evaluation tool that constructs the conceptual framework from a holistic perspective of One Health. Future application of GOHI might promote a common understanding of a strong One Health approach and provide reference for promoting effective measures to strengthen One Health capacity building. With further adaptations under various scenarios, GOHI, along with its technical protocols and databases, will be updated regularly to address current technical limitations, and capture new knowledge.


Subject(s)
One Health , Forecasting , Global Health
2.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-326544

ABSTRACT

Messenger RNA (mRNA) vaccines have shown promise for COVID-19, but still suffer from the critical issue of chemical instability and degradation of the fragile mRNA molecule, which is a major obstacle in the storage, distribution, and efficacy of the vaccine. Previous work showed that thermodynamically more stable mRNAs have higher chemical stability, and this longer half-life, together with optimal codon usage, leads to greater protein expression. Therefore, we aim to design mRNAs with optimized folding stability and codon usage to improve their efficiency. However, the design space is prohibitively large, e.g., there are $\sim\!2.4 \times 10

3.
Proc Natl Acad Sci U S A ; 118(52)2021 12 28.
Article in English | MEDLINE | ID: covidwho-1565770

ABSTRACT

The constant emergence of COVID-19 variants reduces the effectiveness of existing vaccines and test kits. Therefore, it is critical to identify conserved structures in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes as potential targets for variant-proof diagnostics and therapeutics. However, the algorithms to predict these conserved structures, which simultaneously fold and align multiple RNA homologs, scale at best cubically with sequence length and are thus infeasible for coronaviruses, which possess the longest genomes (∼30,000 nt) among RNA viruses. As a result, existing efforts on modeling SARS-CoV-2 structures resort to single-sequence folding as well as local folding methods with short window sizes, which inevitably neglect long-range interactions that are crucial in RNA functions. Here we present LinearTurboFold, an efficient algorithm for folding RNA homologs that scales linearly with sequence length, enabling unprecedented global structural analysis on SARS-CoV-2. Surprisingly, on a group of SARS-CoV-2 and SARS-related genomes, LinearTurboFold's purely in silico prediction not only is close to experimentally guided models for local structures, but also goes far beyond them by capturing the end-to-end pairs between 5' and 3' untranslated regions (UTRs) (∼29,800 nt apart) that match perfectly with a purely experimental work. Furthermore, LinearTurboFold identifies undiscovered conserved structures and conserved accessible regions as potential targets for designing efficient and mutation-insensitive small-molecule drugs, antisense oligonucleotides, small interfering RNAs (siRNAs), CRISPR-Cas13 guide RNAs, and RT-PCR primers. LinearTurboFold is a general technique that can also be applied to other RNA viruses and full-length genome studies and will be a useful tool in fighting the current and future pandemics.


Subject(s)
Algorithms , RNA, Viral/chemistry , SARS-CoV-2/chemistry , Betacoronavirus/chemistry , Betacoronavirus/genetics , Conserved Sequence , Genome, Viral , Mutation , Nucleic Acid Conformation , RNA Folding , RNA, Viral/genetics , SARS-CoV-2/genetics , Sequence Alignment
4.
Biosens Bioelectron ; 198: 113810, 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1517064

ABSTRACT

Exploring reliable and highly-sensitive SARS-CoV-2 antibody diagnosis by point-of-care (POC) manner, holds great public health significance for extensive COVID-19 screening and controlling. Unfortunately, the currently applied gold based lateral flow immunoassay (GLFIA) may expose both false-negative and false-positive interpretations owing to the sensitivity and specificity limitations, which may cause significant risk and waste of public resources for large population screening. To simultaneously overcome the drawbacks of GLFIA, a novel fluorescent LFIA based on signal amplification and dual-antigen sandwich structure was established with largely improved sensitivity and specificity. The compact three-dimensional incorporation of hydrophobic quantum dots within dendritic affinity templates and multilayer surface derivation guaranteed a high and robust fluorescence of single label, which lowered the false negative rate of GLFIA prominently. A dual-antigen sandwich structure using labeled/immobilized SARS-CoV-2 spike receptor binding domain antigen for capturing total human SARS-CoV-2 antibody was developed, instead of general indirect antibody capturing approach, to reduce the false positive rate of GLFIA. Over 300 cases of COVID-19 negative and 97 cases of COVID-19 positive samples, the current assay revealed a 100% sensitivity and 100% specificity confirmed by both polymerase chain reaction (PCR) and chemiluminescence immunoassay (CLIA), compared with the considerable misinterpretation cases by currently applied GLFIA. The quantitative results verified by receiver operating characteristic curve and other statistical analysis indicated a well-distinguished positive/negative sample groups. The proposed strategy is highly sensitive towards low concentrated SARS-CoV-2 antibody serums and highly specific towards serums from COVID-19 negative persons and patients infected by other viruses.


Subject(s)
Biosensing Techniques , COVID-19 , Quantum Dots , Antibodies, Viral , Humans , Immunoassay , SARS-CoV-2 , Sensitivity and Specificity
6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-291507

ABSTRACT

Messenger RNA (mRNA) vaccines have been successful for COVID-19, but still suffer from the critical issue of chemical instability and degradation of the mRNA molecule, which is a major obstacle in the storage, distribution, and efficiency of the vaccine. Previous work established a correlation between its chemical stability and thermodynamic folding stability, and longer half-life also leads to greater protein expression. Therefore, we aim to design mRNAs with optimal folding stability for more efficient mRNA vaccines. However, due to combinatorial explosion because of synonymous codons, the mRNA design space is prohibitively large, e.g., there are ~$2.4 \times 10

8.
Biomedical Engineering and Clinical Medicine ; 24(2):207-210, 2020.
Article in Chinese | CAB Abstracts | ID: covidwho-1106540

ABSTRACT

To explore scientifically configure medical equipment, standardize distribution of protective materials and manage safely, efficiently in prevention and control of novel coronavirus pneumonia, which comprehensively ensure medical personnel safety and provide support for battle against epidemic. The medical equipment division actively implemented relevant national requirements and coordinated hospital internal, information unblocked and data accuracy. Combined with epidemic character-istics. the needs of key departments were guaranteed based on existing medical equipment and protective materials, and re-fined medical equipment management in emergency situations. The real-time department transfer and scientific management of hospital could effectively respond to risks caused by sudden novel coronavirus pneumonia. In condition of shortage of supplies, hospital was prevented clinical cross-infection and ensured normal operation of medical equipment. which provided reliable and effective medical equipment guarantee. After emergency management during epidemic, summarize effective management and control medical equipment department in special period to ensure overall safe and stable operation at hospital, which has strong practicability and repeatability.

9.
J Mol Diagn ; 23(1): 10-18, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-988428

ABSTRACT

The prevalence and clinical relevance of viremia in patients with coronavirus disease 2019 (COVID-19) have not been well studied. A prospective cohort study was designed to investigate blood viral load and clearance kinetics in 52 patients (median age, 62 years; 31 [59.6%] male) and explore their association with clinical features and outcomes based on a novel one-step RT droplet digital PCR (RT-ddPCR). By using one-step RT-ddPCR, 92.3% (48 of 52) of this cohort was quantitatively detected with viremia. The concordance between the blood and oropharyngeal swab tests was 60.92% (53 of 87). One-step RT-ddPCR was tested with a 3.03% false-positive rate and lower 50% confidence interval of detection at 54.026 copies/mL plasma. There was no reduction in the blood viral load in all critical patients, whereas the general and severe patients exhibited a similar ability to clear the viral load. The viral loads in critical patients were significantly higher than those in their general and severe counterparts. Among the 52 study patients, 30 (58%) were discharged from the hospital. Among half of the 30 discharged patients, blood viral load remained positive, of which 76.9% (10 of 13) completely cleared their blood viral load at follow-up. Meanwhile, none of their close contacts had evidence of infection. Quantitative determination of the blood viral test is of great clinical significance in the management of patients with coronavirus disease 2019.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Severity of Illness Index , Viral Load/methods , Viremia/blood , Adult , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/pathology , Female , Humans , Male , Middle Aged , Oropharynx/virology , Prospective Studies , Real-Time Polymerase Chain Reaction , SARS-CoV-2/growth & development , SARS-CoV-2/immunology , Treatment Outcome , Viremia/mortality
10.
J Med Internet Res ; 22(10): e22299, 2020 10 02.
Article in English | MEDLINE | ID: covidwho-862642

ABSTRACT

BACKGROUND: COVID-19 became a global pandemic not long after its identification in late 2019. The genomes of SARS-CoV-2 are being rapidly sequenced and shared on public repositories. To keep up with these updates, scientists need to frequently refresh and reclean data sets, which is an ad hoc and labor-intensive process. Further, scientists with limited bioinformatics or programming knowledge may find it difficult to analyze SARS-CoV-2 genomes. OBJECTIVE: To address these challenges, we developed CoV-Seq, an integrated web server that enables simple and rapid analysis of SARS-CoV-2 genomes. METHODS: CoV-Seq is implemented in Python and JavaScript. The web server and source code URLs are provided in this article. RESULTS: Given a new sequence, CoV-Seq automatically predicts gene boundaries and identifies genetic variants, which are displayed in an interactive genome visualizer and are downloadable for further analysis. A command-line interface is available for high-throughput processing. In addition, we aggregated all publicly available SARS-CoV-2 sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID), National Center for Biotechnology Information (NCBI), European Nucleotide Archive (ENA), and China National GeneBank (CNGB), and extracted genetic variants from these sequences for download and downstream analysis. The CoV-Seq database is updated weekly. CONCLUSIONS: We have developed CoV-Seq, an integrated web service for fast and easy analysis of custom SARS-CoV-2 sequences. The web server provides an interactive module for the analysis of custom sequences and a weekly updated database of genetic variants of all publicly accessible SARS-CoV-2 sequences. We believe CoV-Seq will help improve our understanding of the genetic underpinnings of COVID-19.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/virology , Data Visualization , Databases, Genetic , Genome, Viral/genetics , Pneumonia, Viral/virology , Software , COVID-19 , Computational Biology , Coronavirus Infections/epidemiology , Humans , Pandemics , Pneumonia, Viral/epidemiology , SARS-CoV-2
11.
Clin Exp Med ; 21(1): 35-39, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-777871

ABSTRACT

With the outbreak of COVID-19 ongoing, this infectious disease has been posing a significant threat to public health. However, we are still relatively inexperienced on recognizing the clinical characteristics of severe COVID-19 and death cases. Therefore, we hereby collected and analyzed a total of 232 cases to illustrate the clinical characteristics of such patients in Wuhan and to find notable marks for early clinical warning. We consider age, comorbidities, platelet count, albumin, D-dimer, LDH, CRP and IL-6 level might be more meaningful marks for COVID-19 prognostic evaluation.


Subject(s)
COVID-19/etiology , Aged , Aged, 80 and over , Blood Cell Count , Blood Chemical Analysis , COVID-19/epidemiology , COVID-19/mortality , China/epidemiology , Comorbidity , Humans , Inflammation/blood , Inflammation/virology , Intensive Care Units , Interleukin-6/blood , Middle Aged , Retrospective Studies
12.
Ann Palliat Med ; 9(5): 3235-3248, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-782585

ABSTRACT

BACKGROUND: Neither a vaccine nor specific therapeutic drugs against 2019 novel coronavirus have been developed. Some studies have shown that Xuebijing injection (XBJ) can exert an anti-inflammatory effect by inhibiting the production of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and other cytokines. This study aimed to investigate the effect of XBJ on coronavirus disease 2019 (COVID-19) and its effects on IL-6 and tumor necrosis alpha TNF-α. METHODS: A total of 42 patients, who were diagnosed with COVID-19 and treated with XBJ combined with routine treatment at Chongqing University Three Gorges Hospital between January 20, 2020, and March 11, 2020, were selected as the observation group. A control group comprising 16 patients who received routine treatment was also established, and cases were matched from the observation group on a 1:1 basis according to age, comorbidities, and mild and severe disease. The clinical symptoms, laboratory test indexes, and changes in computed tomography (CT) scans of patients in the two groups were observed at the time of admission and 7 days after treatment, and the time taken for the patients to produce a negative nucleic acid test was also recorded. RESULTS: There were no significant differences in baseline data between the two groups. After treatment, there were significant improvements in IL-6 levels and body temperature in the observation group as compared with the control group. Particularly in severe patients, the reduction in body temperature in the observation group was greater than that in the control group (P<0.05). A higher number of patients in the observation group showed improved CT imaging results compared with the control group, and the time taken to produce a negative nucleic acid test was shorter in the observation group than in the control group; however, the differences were not statistically significant (P>0.05). Furthermore, there were no significant differences in TNF-α and IL-10 between the two groups. CONCLUSIONS: The results of this study suggest that routine treatment combined with XBJ can better improve the clinical outcomes of COVID-19 patients.


Subject(s)
Coronavirus Infections/drug therapy , Drugs, Chinese Herbal/therapeutic use , Pneumonia, Viral/drug therapy , Adult , Aged , Betacoronavirus , COVID-19 , Case-Control Studies , Coronavirus Infections/immunology , Coronavirus Infections/physiopathology , Female , Fever/physiopathology , Humans , Infusions, Intravenous , Interleukin-10/immunology , Interleukin-6/immunology , Length of Stay , Lung/diagnostic imaging , Male , Middle Aged , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/physiopathology , Respiration, Artificial , Retrospective Studies , SARS-CoV-2 , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Tumor Necrosis Factor-alpha/immunology
13.
Air Qual Atmos Health ; 14(2): 217-233, 2021.
Article in English | MEDLINE | ID: covidwho-761545

ABSTRACT

UVB in sunlight, 290-315 nm, can inactivate SARS CoV and SARS CoV-2 viruses on surfaces and in the air. Laboratory exposure to ultraviolet irradiance in the UVC range inactivates many viruses and bacteria in times less than 30 min. Estimated UVB inactivation doses from sunlight in J/m2 are obtained from UVC measurements and radiative transfer calculations, weighted by a virus inactivation action spectrum, using OMI satellite atmospheric data for ozone, clouds, and aerosols. For SARS CoV, using an assumed UVC dose near the mid-range of measured values, D 90 = 40 J/m2, 90% inactivation times T 90 are estimated for exposure to midday 10:00-14:00 direct plus diffuse sunlight and for nearby locations in the shade (diffuse UVB only). For the assumed D 90 = 40 J/m2 model applicable to SARS CoV viruses, calculated estimates show that near noon 11:00-13:00 clear-sky direct sunlight gives values of T 90 < 90 min for mid-latitude sites between March and September and less than 60 min for many equatorial sites for 12 months of the year. Recent direct measurements of UVB sunlight inactivation of the SARS CoV-2 virus that causes COVID-19 show shorter T 90 inactivation times less than 10 min depending on latitude, season, and hour. The equivalent UVC 254 nm D 90 dose for SARS CoV-2 is estimated as 3.2 ± 0.7 J/m2 for viruses on a steel mesh surface and 6.5 ± 1.4 J/m2 for viruses in a growth medium. For SARS CoV-2 clear-sky T 90 on a surface ranges from 4 min in the equatorial zone to less than 30 min in a geographic area forming a near circle with solar zenith angle < 60O centered on the subsolar point for local solar times from 09:00 to 15:00 h.

14.
J Allergy Clin Immunol ; 146(1): 137-146.e3, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-637807

ABSTRACT

BACKGROUND: Accumulating evidence proposed Janus-associated kinase (JAK) inhibitors as therapeutic targets warranting rapid investigation. OBJECTIVE: This study evaluated the efficacy and safety of ruxolitinib, a JAK1/2 inhibitor, for coronavirus disease 2019. METHODS: We conducted a prospective, multicenter, single-blind, randomized controlled phase II trial involving patients with severe coronavirus disease 2019. RESULTS: Forty-three patients were randomly assigned (1:1) to receive ruxolitinib plus standard-of-care treatment (22 patients) or placebo based on standard-of-care treatment (21 patients). After exclusion of 2 patients (1 ineligible, 1 consent withdrawn) from the ruxolitinib group, 20 patients in the intervention group and 21 patients in the control group were included in the study. Treatment with ruxolitinib plus standard-of-care was not associated with significantly accelerated clinical improvement in severe patients with coronavirus disease 2019, although ruxolitinib recipients had a numerically faster clinical improvement. Eighteen (90%) patients from the ruxolitinib group showed computed tomography improvement at day 14 compared with 13 (61.9%) patients from the control group (P = .0495). Three patients in the control group died of respiratory failure, with 14.3% overall mortality at day 28; no patients died in the ruxolitinib group. Ruxolitinib was well tolerated with low toxicities and no new safety signals. Levels of 7 cytokines were significantly decreased in the ruxolitinib group in comparison to the control group. CONCLUSIONS: Although no statistical difference was observed, ruxolitinib recipients had a numerically faster clinical improvement. Significant chest computed tomography improvement, a faster recovery from lymphopenia, and favorable side-effect profile in the ruxolitinib group were encouraging and informative to future trials to test efficacy of ruxolitinib in a larger population.


Subject(s)
Coronavirus Infections/drug therapy , Janus Kinase Inhibitors/therapeutic use , Pneumonia, Viral/drug therapy , Pyrazoles/therapeutic use , Aged , Betacoronavirus , COVID-19 , Coronavirus Infections/mortality , Female , Humans , Male , Middle Aged , Nitriles , Pandemics , Pneumonia, Viral/mortality , Pyrimidines , SARS-CoV-2 , Single-Blind Method , Treatment Outcome
15.
Zhongguo Yi Liao Qi Xie Za Zhi ; 44(3): 263-266, 2020 Mar 08.
Article in Chinese | MEDLINE | ID: covidwho-634810

ABSTRACT

This article researches how to allocate medical protective consumables in hospital and ensure the safety of emergency marketing procurement under the condition that people are easily susceptible to COVID-19. To inform medical staffs about the standard instruction, we establish the corresponding hierarchical control management system and standards of medical protective consumables. To reduce the stress of clinical medical staff and prevent excessive protection, we enhance the training mechanisms and promote the superior normative guidance. The aim is to fully play the effectiveness of the key departments of medical protective consumables, reduce the risk of infection of clinical medical staff and ensure the safety of medical staffs.


Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , COVID-19 , Humans , SARS-CoV-2
16.
Cell Mol Immunol ; 17(9): 992-994, 2020 09.
Article in English | MEDLINE | ID: covidwho-630398
17.
Cancer Sci ; 111(9): 3379-3385, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-622503

ABSTRACT

The rapid spread of coronavirus disease 2019 (COVID-19) represented the most serious issue to public health globally. Hematological patients as immunocompromised hosts are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There is little information available regarding the clinical features of hematological patients concomitant with COVID-19. In this study, 9 concomitant patients were analyzed for their clinical manifestations, laboratory data, radiological findings, and immunologic features. The median age was 50 years (range, 17-68 years) and 6 patients were male. Seven patients were infected through hospital-associated transmission and other 2 through community-associated transmission. Onset of COVID-19 in all patients occurred during routine treatments for their hematological diseases. Eight patients were classified as moderate and 1 patient as critically ill COVID-19. Four patients died, 1 from leukemia progression, 2 from life-threatening secondary infection, and the other from respiratory failure caused by COVID-19. Abruptly elevated levels of cytokines were often correlated with progressive hematological disease or concurrent bacterial infections. Two patients had atypical computed tomography (CT) imaging findings of COVID-19. The median interval from the first CT scan imaging to improvement in survivors was 40 days (range, 14-51 days). Four of 5 survivors had negative serological tests 1 month after symptom onset. Positive viral load in 4 survivors lasted longer than 45 days. Our results indicated concomitant patients formed a distinct subgroup characterized by atypical clinical features, defective viral clearance, and lower level of SARS-CoV-2-specific Abs. Targeted therapies that impair host humoral immunity should be avoided. These findings will be helpful to tailor appropriate management for the concomitant patients.


Subject(s)
Coronavirus Infections/complications , Hematologic Diseases/complications , Hematologic Diseases/therapy , Immunocompromised Host , Pneumonia, Viral/complications , Adolescent , Adult , Aged , COVID-19 , Coronavirus Infections/immunology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/immunology , Young Adult
18.
Genes Dis ; 7(4): 567-577, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-459547

ABSTRACT

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to disperse globally with worrisome speed, identifying amino acid variations in the virus could help to understand the characteristics of it. Here, we studied 489 SARS-CoV-2 genomes obtained from 32 countries from the Nextstrain database and performed phylogenetic tree analysis by clade, country, and genotype of the surface spike glycoprotein (S protein) at site 614. We found that virus strains from mainland China were mostly distributed in Clade B and Clade undefined in the phylogenetic tree, with very few found in Clade A. In contrast, Clades A2 (one case) and A2a (112 cases) predominantly contained strains from European regions. Moreover, Clades A2 and A2a differed significantly from those of mainland China in age of infected population (P = 0.0071, mean age 40.24 to 46.66), although such differences did not exist between the US and mainland China. Further analysis demonstrated that the variation of the S protein at site 614 (QHD43416.1: p.614D>G) was a characteristic of stains in Clades A2 and A2a. Importantly, this variation was predicted to have neutral or benign effects on the function of the S protein. In addition, global quality estimates and 3D protein structures tended to be different between the two S proteins. In summary, we identified different genomic epidemiology among SARS-CoV-2 strains in different clades, especially in an amino acid variation of the S protein at 614, revealing potential viral genome divergence in SARS-CoV-2 strains.

19.
Preprint in English | bioRxiv | ID: ppbiorxiv-116020

ABSTRACT

The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global threat to human health. Using a multidisciplinary approach, we identified and validated the hepatitis C virus (HCV) protease inhibitor simeprevir as an especially promising repurposable drug for treating COVID-19. Simeprevir potently reduces SARS-CoV-2 viral load by multiple orders of magnitude and synergizes with remdesivir in vitro. Mechanistically, we showed that simeprevir inhibits the main protease (Mpro) and unexpectedly the RNA-dependent RNA polymerase (RdRp). Our results thus reveal the viral protein targets of simeprevir, and provide preclinical rationale for the combination of simeprevir and remdesivir for the pharmacological management of COVID-19 patients. One Sentence SummaryDiscovery of simeprevir as a potent suppressor of SARS-CoV-2 viral replication that synergizes with remdesivir.

20.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(2): 168-170, 2020 Feb 29.
Article in Chinese | MEDLINE | ID: covidwho-258206

ABSTRACT

In the ongoing fight against the epidemic of COVID-19, the medical staff has been under tremendous pressure. Wearing the protective equipment (masks, goggles, and protective screens) with a poor breathability for a long time causes various skin problems, such as allergies, excessive skin hydration, local mechanical injuries, and even secondary infections. In addition, in a closed environment, compression and friction aggravate skin reactions, which may compromise duty performance of the medical staff. It is therefore essential to provide timely treatment opinions and prevention methods for common skin problems. We also give suggestions concerning the preparation of medical kit for skin protection in the epidemic area.


Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Personal Protective Equipment , Pneumonia, Viral , Skin Diseases , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Humans , Pandemics/prevention & control , Personal Protective Equipment/adverse effects , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , SARS-CoV-2 , Skin Diseases/etiology , Skin Diseases/therapy
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