Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 13 de 13
Filter
1.
J Virol ; 96(2): e0106321, 2022 01 26.
Article in English | MEDLINE | ID: covidwho-1476388

ABSTRACT

COVID-19 affects multiple organs. Clinical data from the Mount Sinai Health System show that substantial numbers of COVID-19 patients without prior heart disease develop cardiac dysfunction. How COVID-19 patients develop cardiac disease is not known. We integrated cell biological and physiological analyses of human cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the presence of interleukins (ILs) with clinical findings related to laboratory values in COVID-19 patients to identify plausible mechanisms of cardiac disease in COVID-19 patients. We infected hiPSC-derived cardiomyocytes from healthy human subjects with SARS-CoV-2 in the absence and presence of IL-6 and IL-1ß. Infection resulted in increased numbers of multinucleated cells. Interleukin treatment and infection resulted in disorganization of myofibrils, extracellular release of troponin I, and reduced and erratic beating. Infection resulted in decreased expression of mRNA encoding key proteins of the cardiomyocyte contractile apparatus. Although interleukins did not increase the extent of infection, they increased the contractile dysfunction associated with viral infection of cardiomyocytes, resulting in cessation of beating. Clinical data from hospitalized patients from the Mount Sinai Health System show that a significant portion of COVID-19 patients without history of heart disease have elevated troponin and interleukin levels. A substantial subset of these patients showed reduced left ventricular function by echocardiography. Our laboratory observations, combined with the clinical data, indicate that direct effects on cardiomyocytes by interleukins and SARS-CoV-2 infection might underlie heart disease in COVID-19 patients. IMPORTANCE SARS-CoV-2 infects multiple organs, including the heart. Analyses of hospitalized patients show that a substantial number without prior indication of heart disease or comorbidities show significant injury to heart tissue, assessed by increased levels of troponin in blood. We studied the cell biological and physiological effects of virus infection of healthy human iPSC-derived cardiomyocytes in culture. Virus infection with interleukins disorganizes myofibrils, increases cell size and the numbers of multinucleated cells, and suppresses the expression of proteins of the contractile apparatus. Viral infection of cardiomyocytes in culture triggers release of troponin similar to elevation in levels of COVID-19 patients with heart disease. Viral infection in the presence of interleukins slows down and desynchronizes the beating of cardiomyocytes in culture. The cell-level physiological changes are similar to decreases in left ventricular ejection seen in imaging of patients' hearts. These observations suggest that direct injury to heart tissue by virus can be one underlying cause of heart disease in COVID-19.


Subject(s)
COVID-19/immunology , Induced Pluripotent Stem Cells , Interleukin-10/immunology , Interleukin-1beta/immunology , Interleukin-6/immunology , Myocytes, Cardiac , Cells, Cultured , Humans , Induced Pluripotent Stem Cells/immunology , Induced Pluripotent Stem Cells/pathology , Induced Pluripotent Stem Cells/virology , Myocytes, Cardiac/immunology , Myocytes, Cardiac/pathology , Myocytes, Cardiac/virology
2.
Nat Commun ; 12(1): 6055, 2021 10 18.
Article in English | MEDLINE | ID: covidwho-1475294

ABSTRACT

COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is a virally encoded protein that is essential across a broad spectrum of coronaviruses with no close human analogs. PF-00835231, a 3CL protease inhibitor, has exhibited potent in vitro antiviral activity against SARS-CoV-2 as a single agent. Here we report, the design and characterization of a phosphate prodrug PF-07304814 to enable the delivery and projected sustained systemic exposure in human of PF-00835231 to inhibit coronavirus family 3CL protease activity with selectivity over human host protease targets. Furthermore, we show that PF-00835231 has additive/synergistic activity in combination with remdesivir. We present the ADME, safety, in vitro, and in vivo antiviral activity data that supports the clinical evaluation of PF-07304814 as a potential COVID-19 treatment.


Subject(s)
COVID-19/drug therapy , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus Protease Inhibitors/administration & dosage , Indoles/administration & dosage , Leucine/administration & dosage , Pyrrolidinones/administration & dosage , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/adverse effects , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacokinetics , Alanine/administration & dosage , Alanine/adverse effects , Alanine/analogs & derivatives , Alanine/pharmacokinetics , Animals , COVID-19/virology , Chlorocebus aethiops , Coronavirus 229E, Human/drug effects , Coronavirus 229E, Human/enzymology , Coronavirus Protease Inhibitors/adverse effects , Coronavirus Protease Inhibitors/pharmacokinetics , Disease Models, Animal , Drug Design , Drug Synergism , Drug Therapy, Combination , HeLa Cells , Humans , Indoles/adverse effects , Indoles/pharmacokinetics , Infusions, Intravenous , Leucine/adverse effects , Leucine/pharmacokinetics , Mice , Pyrrolidinones/adverse effects , Pyrrolidinones/pharmacokinetics , SARS Virus/drug effects , SARS Virus/enzymology , SARS-CoV-2/drug effects , SARS-CoV-2/enzymology , Vero Cells
3.
Science ; 373(6554): 541-547, 2021 07 30.
Article in English | MEDLINE | ID: covidwho-1334531

ABSTRACT

Repurposing drugs as treatments for COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has drawn much attention. Beginning with sigma receptor ligands and expanding to other drugs from screening in the field, we became concerned that phospholipidosis was a shared mechanism underlying the antiviral activity of many repurposed drugs. For all of the 23 cationic amphiphilic drugs we tested, including hydroxychloroquine, azithromycin, amiodarone, and four others already in clinical trials, phospholipidosis was monotonically correlated with antiviral efficacy. Conversely, drugs active against the same targets that did not induce phospholipidosis were not antiviral. Phospholipidosis depends on the physicochemical properties of drugs and does not reflect specific target-based activities-rather, it may be considered a toxic confound in early drug discovery. Early detection of phospholipidosis could eliminate these artifacts, enabling a focus on molecules with therapeutic potential.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Drug Repositioning , Lipidoses/chemically induced , Phospholipids/metabolism , SARS-CoV-2/drug effects , A549 Cells , Animals , Antiviral Agents/chemistry , Antiviral Agents/therapeutic use , Antiviral Agents/toxicity , COVID-19/virology , Cations , Chlorocebus aethiops , Dose-Response Relationship, Drug , Female , Humans , Mice , Microbial Sensitivity Tests , SARS-CoV-2/physiology , Surface-Active Agents/chemistry , Surface-Active Agents/pharmacology , Surface-Active Agents/toxicity , Vero Cells , Virus Replication/drug effects
4.
Sci Rep ; 11(1): 12310, 2021 06 10.
Article in English | MEDLINE | ID: covidwho-1265969

ABSTRACT

The novel SARS-CoV-2 virus emerged in December 2019 and has few effective treatments. We applied a computational drug repositioning pipeline to SARS-CoV-2 differential gene expression signatures derived from publicly available data. We utilized three independent published studies to acquire or generate lists of differentially expressed genes between control and SARS-CoV-2-infected samples. Using a rank-based pattern matching strategy based on the Kolmogorov-Smirnov Statistic, the signatures were queried against drug profiles from Connectivity Map (CMap). We validated 16 of our top predicted hits in live SARS-CoV-2 antiviral assays in either Calu-3 or 293T-ACE2 cells. Validation experiments in human cell lines showed that 11 of the 16 compounds tested to date (including clofazimine, haloperidol and others) had measurable antiviral activity against SARS-CoV-2. These initial results are encouraging as we continue to work towards a further analysis of these predicted drugs as potential therapeutics for the treatment of COVID-19.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Drug Repositioning/methods , SARS-CoV-2/drug effects , Transcriptome/drug effects , COVID-19/genetics , Computational Biology/methods , Humans , SARS-CoV-2/physiology
5.
Front Pharmacol ; 12: 633680, 2021.
Article in English | MEDLINE | ID: covidwho-1175552

ABSTRACT

SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. SARS-CoV-2 infection is necessary but not sufficient for development of clinical COVID-19 disease. Currently, there are no approved pre- or post-exposure prophylactic COVID-19 medical countermeasures. Clinical data suggest that famotidine may mitigate COVID-19 disease, but both mechanism of action and rationale for dose selection remain obscure. We have investigated several plausible hypotheses for famotidine activity including antiviral and host-mediated mechanisms of action. We propose that the principal mechanism of action of famotidine for relieving COVID-19 symptoms involves on-target histamine receptor H2 activity, and that development of clinical COVID-19 involves dysfunctional mast cell activation and histamine release. Based on these findings and associated hypothesis, new COVID-19 multi-drug treatment strategies based on repurposing well-characterized drugs are being developed and clinically tested, and many of these drugs are available worldwide in inexpensive generic oral forms suitable for both outpatient and inpatient treatment of COVID-19 disease.

6.
Science ; 371(6532): 926-931, 2021 02 26.
Article in English | MEDLINE | ID: covidwho-1048642

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins interact with the eukaryotic translation machinery, and inhibitors of translation have potent antiviral effects. We found that the drug plitidepsin (aplidin), which has limited clinical approval, possesses antiviral activity (90% inhibitory concentration = 0.88 nM) that is more potent than remdesivir against SARS-CoV-2 in vitro by a factor of 27.5, with limited toxicity in cell culture. Through the use of a drug-resistant mutant, we show that the antiviral activity of plitidepsin against SARS-CoV-2 is mediated through inhibition of the known target eEF1A (eukaryotic translation elongation factor 1A). We demonstrate the in vivo efficacy of plitidepsin treatment in two mouse models of SARS-CoV-2 infection with a reduction of viral replication in the lungs by two orders of magnitude using prophylactic treatment. Our results indicate that plitidepsin is a promising therapeutic candidate for COVID-19.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Depsipeptides/pharmacology , Peptide Elongation Factor 1/antagonists & inhibitors , SARS-CoV-2/drug effects , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacology , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/pharmacology , Alanine/therapeutic use , Animals , Antiviral Agents/therapeutic use , COVID-19/prevention & control , COVID-19/virology , Coronavirus Nucleocapsid Proteins/biosynthesis , Coronavirus Nucleocapsid Proteins/genetics , Depsipeptides/administration & dosage , Depsipeptides/therapeutic use , Drug Evaluation, Preclinical , Female , HEK293 Cells , Humans , Lung/virology , Mice, Inbred C57BL , Mutation , Peptides, Cyclic , Phosphoproteins/biosynthesis , Phosphoproteins/genetics , RNA, Viral/biosynthesis , RNA, Viral/genetics , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Virus Replication/drug effects
7.
Science ; 370(6523): 1473-1479, 2020 12 18.
Article in English | MEDLINE | ID: covidwho-913670

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells via an interaction between its Spike protein and the host cell receptor angiotensin-converting enzyme 2 (ACE2). By screening a yeast surface-displayed library of synthetic nanobody sequences, we developed nanobodies that disrupt the interaction between Spike and ACE2. Cryo-electron microscopy (cryo-EM) revealed that one nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains locked into their inaccessible down state, incapable of binding ACE2. Affinity maturation and structure-guided design of multivalency yielded a trivalent nanobody, mNb6-tri, with femtomolar affinity for Spike and picomolar neutralization of SARS-CoV-2 infection. mNb6-tri retains function after aerosolization, lyophilization, and heat treatment, which enables aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Single-Domain Antibodies/immunology , Spike Glycoprotein, Coronavirus/immunology , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/immunology , Animals , Antibodies, Neutralizing/chemistry , Antibodies, Viral/chemistry , Antibody Affinity , Chlorocebus aethiops , Cryoelectron Microscopy , Humans , Neutralization Tests , Protein Binding , Protein Stability , Single-Domain Antibodies/chemistry , Spike Glycoprotein, Coronavirus/chemistry , Vero Cells
8.
Proc Natl Acad Sci U S A ; 117(45): 28344-28354, 2020 11 10.
Article in English | MEDLINE | ID: covidwho-887237

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic that is a serious global health problem. Evasion of IFN-mediated antiviral signaling is a common defense strategy that pathogenic viruses use to replicate and propagate in their host. In this study, we show that SARS-CoV-2 is able to efficiently block STAT1 and STAT2 nuclear translocation in order to impair transcriptional induction of IFN-stimulated genes (ISGs). Our results demonstrate that the viral accessory protein Orf6 exerts this anti-IFN activity. We found that SARS-CoV-2 Orf6 localizes at the nuclear pore complex (NPC) and directly interacts with Nup98-Rae1 via its C-terminal domain to impair docking of cargo-receptor (karyopherin/importin) complex and disrupt nuclear import. In addition, we show that a methionine-to-arginine substitution at residue 58 impairs Orf6 binding to the Nup98-Rae1 complex and abolishes its IFN antagonistic function. All together our data unravel a mechanism of viral antagonism in which a virus hijacks the Nup98-Rae1 complex to overcome the antiviral action of IFN.


Subject(s)
COVID-19/metabolism , Interferons/metabolism , Nuclear Pore Complex Proteins/metabolism , Nuclear Pore/metabolism , STAT1 Transcription Factor/metabolism , STAT2 Transcription Factor/metabolism , Viral Proteins/metabolism , Active Transport, Cell Nucleus , Animals , Binding Sites , Chlorocebus aethiops , HEK293 Cells , Humans , Nuclear Matrix-Associated Proteins/chemistry , Nuclear Matrix-Associated Proteins/metabolism , Nucleocytoplasmic Transport Proteins/chemistry , Nucleocytoplasmic Transport Proteins/metabolism , Protein Binding , Signal Transduction , Vero Cells
9.
Nature ; 586(7827): 113-119, 2020 10.
Article in English | MEDLINE | ID: covidwho-672174

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 has triggered an ongoing global pandemic of the severe pneumonia-like disease coronavirus disease 2019 (COVID-19)1. The development of a vaccine is likely to take at least 12-18 months, and the typical timeline for approval of a new antiviral therapeutic agent can exceed 10 years. Thus, repurposing of known drugs could substantially accelerate the deployment of new therapies for COVID-19. Here we profiled a library of drugs encompassing approximately 12,000 clinical-stage or Food and Drug Administration (FDA)-approved small molecules to identify candidate therapeutic drugs for COVID-19. We report the identification of 100 molecules that inhibit viral replication of SARS-CoV-2, including 21 drugs that exhibit dose-response relationships. Of these, thirteen were found to harbour effective concentrations commensurate with probable achievable therapeutic doses in patients, including the PIKfyve kinase inhibitor apilimod2-4 and the cysteine protease inhibitors MDL-28170, Z LVG CHN2, VBY-825 and ONO 5334. Notably, MDL-28170, ONO 5334 and apilimod were found to antagonize viral replication in human pneumocyte-like cells derived from induced pluripotent stem cells, and apilimod also demonstrated antiviral efficacy in a primary human lung explant model. Since most of the molecules identified in this study have already advanced into the clinic, their known pharmacological and human safety profiles will enable accelerated preclinical and clinical evaluation of these drugs for the treatment of COVID-19.


Subject(s)
Antiviral Agents/analysis , Antiviral Agents/pharmacology , Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Drug Evaluation, Preclinical , Drug Repositioning , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/pharmacology , Alanine/analogs & derivatives , Alanine/pharmacology , Alveolar Epithelial Cells/cytology , Alveolar Epithelial Cells/drug effects , Betacoronavirus/growth & development , COVID-19 , Cell Line , Cysteine Proteinase Inhibitors/analysis , Cysteine Proteinase Inhibitors/pharmacology , Dose-Response Relationship, Drug , Drug Synergism , Gene Expression Regulation/drug effects , Humans , Hydrazones , Induced Pluripotent Stem Cells/cytology , Models, Biological , Morpholines/analysis , Morpholines/pharmacology , Pandemics , Pyrimidines , Reproducibility of Results , SARS-CoV-2 , Small Molecule Libraries/analysis , Small Molecule Libraries/pharmacology , Triazines/analysis , Triazines/pharmacology , Virus Internalization/drug effects , Virus Replication/drug effects
10.
Res Sq ; 2020 Jun 22.
Article in English | MEDLINE | ID: covidwho-671001

ABSTRACT

SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. Currently, there are no pre- or post-exposure prophylactic COVID-19 medical countermeasures. Clinical data suggest that famotidine may mitigate COVID-19 disease, but both mechanism of action and rationale for dose selection remain obscure. We explore several plausible avenues of activity including antiviral and host-mediated actions. We propose that the principal famotidine mechanism of action for COVID-19 involves on-target histamine receptor H 2 activity, and that development of clinical COVID-19 involves dysfunctional mast cell activation and histamine release.

11.
Cell ; 182(3): 685-712.e19, 2020 08 06.
Article in English | MEDLINE | ID: covidwho-624826

ABSTRACT

The causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions and killed hundreds of thousands of people worldwide, highlighting an urgent need to develop antiviral therapies. Here we present a quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells, revealing dramatic rewiring of phosphorylation on host and viral proteins. SARS-CoV-2 infection promoted casein kinase II (CK2) and p38 MAPK activation, production of diverse cytokines, and shutdown of mitotic kinases, resulting in cell cycle arrest. Infection also stimulated a marked induction of CK2-containing filopodial protrusions possessing budding viral particles. Eighty-seven drugs and compounds were identified by mapping global phosphorylation profiles to dysregulated kinases and pathways. We found pharmacologic inhibition of the p38, CK2, CDK, AXL, and PIKFYVE kinases to possess antiviral efficacy, representing potential COVID-19 therapies.


Subject(s)
Betacoronavirus/metabolism , Coronavirus Infections/metabolism , Drug Evaluation, Preclinical/methods , Pneumonia, Viral/metabolism , Proteomics/methods , A549 Cells , Angiotensin-Converting Enzyme 2 , Animals , Antiviral Agents/pharmacology , COVID-19 , Caco-2 Cells , Casein Kinase II/antagonists & inhibitors , Casein Kinase II/metabolism , Chlorocebus aethiops , Coronavirus Infections/virology , Cyclin-Dependent Kinases/antagonists & inhibitors , Cyclin-Dependent Kinases/metabolism , HEK293 Cells , Host-Pathogen Interactions , Humans , Pandemics , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Phosphoinositide-3 Kinase Inhibitors/pharmacology , Phosphorylation , Pneumonia, Viral/virology , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins/antagonists & inhibitors , Proto-Oncogene Proteins/metabolism , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Receptor Protein-Tyrosine Kinases/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , p38 Mitogen-Activated Protein Kinases/metabolism
12.
Curr Protoc Microbiol ; 58(1): e108, 2020 09.
Article in English | MEDLINE | ID: covidwho-614201

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the city of Wuhan, Hubei Province, China, in late 2019. Since then, the virus has spread globally and caused a pandemic. Assays that can measure the antiviral activity of antibodies or antiviral compounds are needed for SARS-CoV-2 vaccine and drug development. Here, we describe in detail a microneutralization assay, which can be used to assess in a quantitative manner if antibodies or drugs can block entry and/or replication of SARS-CoV-2 in vitro. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Microneutralization assay to test inhibition of virus by antibodies (purified antibodies or serum/plasma) Basic Protocol 2: Screening of anti-SARS-CoV-2 compounds in vitro Support Protocol: SARS-CoV-2 propagation.


Subject(s)
Antibodies, Viral/immunology , Betacoronavirus/immunology , Drug Evaluation, Preclinical/methods , Neutralization Tests/methods , Animals , COVID-19 , Chlorocebus aethiops , Coronavirus Infections/immunology , Coronavirus Infections/virology , Humans , Mice , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Vero Cells , Virus Internalization/drug effects , Virus Replication/drug effects
13.
Nature ; 583(7816): 459-468, 2020 07.
Article in English | MEDLINE | ID: covidwho-152254

ABSTRACT

A newly described coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than 160,000 individuals and caused worldwide social and economic disruption1,2. There are no antiviral drugs with proven clinical efficacy for the treatment of COVID-19, nor are there any vaccines that prevent infection with SARS-CoV-2, and efforts to develop drugs and vaccines are hampered by the limited knowledge of the molecular details of how SARS-CoV-2 infects cells. Here we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins that physically associated with each of the SARS-CoV-2 proteins using affinity-purification mass spectrometry, identifying 332 high-confidence protein-protein interactions between SARS-CoV-2 and human proteins. Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (of which, 29 drugs are approved by the US Food and Drug Administration, 12 are in clinical trials and 28 are preclinical compounds). We screened a subset of these in multiple viral assays and found two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the sigma-1 and sigma-2 receptors. Further studies of these host-factor-targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.


Subject(s)
Betacoronavirus/drug effects , Coronavirus Infections/drug therapy , Coronavirus Infections/metabolism , Drug Repositioning , Molecular Targeted Therapy , Pneumonia, Viral/drug therapy , Pneumonia, Viral/metabolism , Protein Interaction Maps , Viral Proteins/metabolism , Animals , Antiviral Agents/classification , Antiviral Agents/pharmacology , Betacoronavirus/genetics , Betacoronavirus/metabolism , Betacoronavirus/pathogenicity , COVID-19 , Chlorocebus aethiops , Cloning, Molecular , Coronavirus Infections/immunology , Coronavirus Infections/virology , Drug Evaluation, Preclinical , HEK293 Cells , Host-Pathogen Interactions/drug effects , Humans , Immunity, Innate , Mass Spectrometry , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Protein Binding , Protein Biosynthesis/drug effects , Protein Domains , Protein Interaction Mapping , Receptors, sigma/metabolism , SARS-CoV-2 , SKP Cullin F-Box Protein Ligases/metabolism , Vero Cells , Viral Proteins/genetics
SELECTION OF CITATIONS
SEARCH DETAIL