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SARS-CoV-2 proteins

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    Broad-spectrum, patient-adaptable inhaled niclosamide-lysozyme particles are efficacious against coronaviruses in lethal murine infection models

    Authors: Ashlee D Brunaugh; Hyojong Seo; Zachary Warnken; Li Ding; Sang Heui Seo; Hugh D.C. Smyth; Justin Rafa O De La Fuente; Megan Mathew; Desmond Green; Sayari Patel; Maria Virginia Perez Bastidas; Sara Haddadi; Mukunthan Murthi; Miguel Santiago Gonzalez; Shweta Kambali; Kayo HM Santos; Huda Asif; Farzaneh Modarresi; Mohammad Faghihi; Mehdi Mirsaeidi

    doi:10.1101/2020.09.24.310490 Date: 2020-09-24 Source: bioRxiv

    Niclosamide (NIC) has demonstrated promising in vitro antiviral efficacy against SARS-CoV-2, the causative agent of the COVID-19 MESHD COVID-19 MESHD pandemic. Though NIC is already FDA-approved, the oral formulation produces systemic drug levels that are too low to inhibit SARS-CoV-2. As an alternative, direct delivery of NIC to the respiratory tract as an aerosol could target the primary site of for SARS-CoV-2 acquisition MESHD and spread. We have developed a niclosamide powder suitable for delivery via dry powder inhaler, nebulizer, and nasal spray through the incorporation of human lysozyme (hLYS) as a carrier molecule. This novel formulation exhibits potent in vitro and in vivo activity against MERS-CoV and SARS-CoV-2 and protects against methicillin-resistance staphylococcus aureus pneumonia MESHD and inflammatory lung damage MESHD. The suitability of the formulation for all stages of the disease and low-cost development approach will ensure wide-spread utilization.

    Surgical masks decontamination for reuse by members of the public: feasibility study and development of home-based methods

    Authors: Cheok Hong, Mun; Sook Lan, Tan; Soo Zeng Fiona, Phua; Wei Qi, Lim; Shyue Wei, Pang; Vidhya, Novem; Geraldine, Chee; Yi Hui Shermin, Soh

    doi:10.21203/rs.3.rs-72875/v1 Date: 2020-09-05 Source: ResearchSquare

    This study aims to propose decontamination methods that are suitable for use by members of the public to cope with the shortage of surgical masks during the current COVID-19 pandemic MESHD COVID-19 pandemic MESHD. 3-ply surgical masks were subjected to different decontamination protocols (heat, chemical, ultraviolet irradiation) to assess their abilities to achieve at least 4-log reduction of two common respiratory pathogens, H1N1 Influenza A virus, a single-stranded RNA enveloped virus similar to SARS-CoV-2 and Staphylococcus aureus, a Gram-positive bacterium that is more resistant to decontamination than single stranded RNA enveloped virus. Decontaminated surgical masks were assessed for differences in breathability, particle filtration efficiency and bacteria filtration efficiency as compared with non-decontaminated masks. The number of decontamination cycles that the 3-ply surgical masks could undergo without significant changes in breathability and filtration efficiencies were also determined. It was found that surgical masks decontaminated by either soaking for 60 min in 0.5% (v/v) aqueous hydrogen peroxide solution, or 30 min of soaking in 0.05% - 0.5% (v/v) aqueous sodium hypochlorite diluted from household bleach or ultraviolet irradiation by a surface dose of 13.5 kJ/m2 were able to achieve at least a 4-log reduction of both Staphylococcus aureus MESHD and H1N1 Influenza A virus spiked on surgical mask test swatches. No significant changes in breathability and filtration efficiencies of the surgical masks were observed after ten decontamination cycles of hydrogen peroxide or diluted bleach treatment or 30 cycles of ultraviolet irradiation. 

    Characterization of Microbial Co-infections in the Respiratory Tract of hospitalized COVID-19 MESHD patients

    Authors: Huanzi Zhong; Yanqun Wang; Zhun Shi; Lu Zhang; Huahui Ren; Weiqun He; Zhaoyong Zhang; Airu Zhu; Jingxian Zhao; Fei Xiao; Fangming Yang; Tianzhu Liang; Feng Ye; Bei Zhong; Shicong Ruan; Mian Gan; Jiahui Zhu; Fang Li; Fuqiang Li; Daxi Wang; Jiandong Li; Peidi Ren; Shida Zhu; Huanming Yang; Jian Wang; Karsten Kristiansen; Hein M Tun; Weijun Chen; Nanshan Zhong; Xun Xu; Yi-min Li; Junhua LI; Jincun Zhao

    doi:10.1101/2020.07.02.20143032 Date: 2020-07-05 Source: medRxiv

    Summary Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus disease 2019 MESHD ( COVID-19 MESHD). However, microbial composition of the respiratory tract and other infected tissues, as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19 MESHD patients remain unclear. Method Between January 27 and February 26, 2020, serial clinical specimens (sputum, nasal and throat swab, anal swab and feces) were collected from a cohort of hospitalized COVID-19 MESHD patients, including 8 mildly and 15 severely ill patients (requiring ICU admission and mechanical ventilation), in the Guangdong province, China. Total RNA was extracted and ultra-deep metatranscriptomic sequencing was performed in combination with laboratory diagnostic assays. Co-infection MESHD rates, the prevalence and abundance of microbial communities in these COVID-19 MESHD patients were determined. Findings Notably, respiratory microbial co-infections MESHD were exclusively found in 84.6% of severely ill patients (11/13), among which viral and bacterial co-infections MESHD were detected by sequencing in 30.8% (4/13) and 69.2% (9/13) of the patients, respectively. In addition, for 23.1% (3/13) of the patients, bacterial co-infections MESHD with Burkholderia cepacia complex (BCC) and Staphylococcus epidermidis MESHD were also confirmed by bacterial culture. Further, a time-dependent, secondary infection of B. cenocepacia with expressions of multiple virulence genes in one severely ill patient was demonstrated, which might be the primary cause of his disease deterioration and death MESHD one month after ICU admission. Interpretation Our findings identified distinct patterns of co-infections MESHD with SARS-CoV-2 and various respiratory pathogenic microbes in hospitalized COVID-19 MESHD patients in relation to disease severity. Detection and tracking of BCC-associated nosocomial infections MESHD are recommended to improve the pre-emptive treatment regimen and reduce fatal outcomes of hospitalized patients infected with SARS-CoV-2. Funding National Science and Technology Major Project of China, National Major Project for Control and Prevention of Infectious Disease MESHD in China, the emergency grants for prevention and control of SARS-CoV-2 of Ministry of Science and Technology and Guangdong province, Guangdong Provincial Key Laboratory of Genome Read and Write, Guangdong Provincial Academician Workstation of BGI Synthetic Genomics, and Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics.

    Vaporized H2O2 decontamination against surrogate viruses for the reuse of N95 respirators in the COVID-19 MESHD emergency

    Authors: Ebru Oral; Keith K Wannomae; Rachel L Connolly; Joseph A Gardecki; Hui Min Leung; Orhun K Muratoglu; John Durkin; Ralph Jones; Cassidy Collins; Julian Gjore; Amanda Budzilowicz; Tareq Jaber

    doi:10.1101/2020.06.25.20140269 Date: 2020-06-28 Source: medRxiv

    Decontamination of N95 respirators has become critical to alleviate PPE shortages for healthcare workers in the current COVID-19 MESHD emergency. The factors that are considered for the effective reuse of these masks are the fit, filter efficiency and decontamination/disinfection level both for SARS-CoV-2, which is the causative virus for COVID-19 MESHD, and for other organisms of concern in the hospital environment such as Staphylococcus aureus MESHD or Clostridium difficile. In its guidance entitled 'Recommendations for Sponsors Requesting EUAs for Decontamination and Bioburden Reduction Systems for Surgical Masks and Respirators During the Coronavirus Disease 2019 MESHD ( COVID19 MESHD) Public Health Emergency' (May 2020)[1], the FDA recommends a 6-log10 reduction in either the most resistant bacterial spores for the system or in a mycobacterium species to authorize the use of a decontamination method of N95 respirators for single or multiple users. While the goal is primarily inactivation against SARS-CoV-2, testing of decontamination methods against the virus may not always be available. For decontamination methods considered for only single users, the recommendation is a 6-log10 reduction in the infective virus concentration of 3 non-enveloped viruses or in the concentration of two Gram (+) and two Gram (-) bacteria. Based on these recommendations, we explored the efficacy of vaporized H2O2 (VHP) treatment of N95 respirators against surrogate viruses covering a wide range of disinfection resistance for emergency decontamination and reuse to alleviate PPE shortages for healthcare workers in the COVID-19 MESHD emergency.

    Hospital-acquired infective endocarditis during Covid-19 MESHD Covid-19 MESHD pandemic

    Authors: Antonio Ramos-Martinez; Ana Fernndez-Cruz; Fernando Dominguez; Alberto Forteza; Marta Cobo; Isabel Sanchez-Romero; Angel asensio

    doi:10.1101/2020.05.17.20101063 Date: 2020-05-22 Source: medRxiv

    Background. The COVID pandemic has had a major impact on healthcare in hospitals, including the diagnosis and treatment of infections. Hospital-acquired infective endocarditis MESHD ( HAIE MESHD) is a severe complication of medical procedures that has shown a progressive increase in recent years. Objectives. to determine whether the incidence of HAIE during the first two months of the epidemic (March-April 2020) was higher than previously observed and to describe the clinical characteristics of these cases. The probability of studied event (HAIE) during the studied period was calculate by Poisson distribution. Results. Four cases of HAIE were diagnosed in our institution during the study period. The incidence of HAIE during the study period was 2/patient-month and 0.25/patient-month during the previous 5 years (p=0.024). Two cases appeared during admission for COVID-19 MESHD with pulmonary involvement treated with metilprednisolone and tocilizumab. The other two cases were admitted to the hospital during the epidemic. All cases underwent central venous and urinary catheterization during admission. The etiology of HAIE was Enterococcus faecalis (2 cases), Staphylococcus aureus MESHD and Candida albicans (one case each). A source of infection was identified in three cases (central venous catheter, peripheral venous catheter, sternal wound infection, respectively). One patient was operated on. There were no fatalities during the first 30 days of follow-up. Conclusion. The incidence of HAIE during COVID-19 pandemic MESHD in our institution was higher than usual. In order to reduce the risk of this serious infection, optimal catheter care, appropriate use of corticosteroids and interleukin antagonists and early treatment of every local infection should be prioritized during coronavirus outbreaks.

    Efficacy of moist heat decontamination against various pathogens for the reuse of N95 respirators in the COVID-19 MESHD emergency

    Authors: Ebru Oral; Keith K Wannomae; Dmitry Gil; Rachel L Connolly; Joseph Gardecki; Hui Min Leung; Orhun K Muratoglu; Amy Tsurumi; Laurence G Rahme; Tareq Jaber; Cassidy Collins; Amanda Budzilowicz; Julian Gjore

    doi:10.1101/2020.05.13.20100651 Date: 2020-05-19 Source: medRxiv

    Decontamination of N95 respirators has become critical to alleviate PPE shortages for healthcare workers in the current COVID-19 MESHD emergency. The factors that are considered for the effective reuse of these masks are the fit, filter efficiency and decontamination/disinfection level both for SARS-CoV2, which is the causative virus for COVID-19 MESHD, and for other organisms of concern in the hospital environment such as Staphylococcus aureus MESHD or Clostridium difficile. The efficacy of inactivation or eradication against various pathogens should be evaluated thoroughly to understand the level of afforded disinfection. Methods commonly used in the sterilization of medical devices such as ionizing radiation, vaporized hydrogen peroxide, and ethylene oxide can provide a high level of disinfection, defined as a 6 log10 reduction, against bacterial spores, considered the most resistant microorganisms. CDC guidance on the decontamination and reuse of N95s also includes the use of moist heat (60{degrees}C, 80% relative humidity, 15-30 min) as a possible recommendation based on literature showing preservation of fit efficiency and inactivation of H1N1 on spiked masks. Here, we explored the efficacy of using moist heat under these conditions as a decontamination method for an N95 respirator (3M 1860S, St. Paul, MN) against various pathogens with different resistance; enveloped RNA viruses, Gram (+/-) bacteria, and non-enveloped viruses.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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