Romel Rosales
A5056558213- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Mosquito-borne diseases and control
- Computational Drug Discovery Methods
- Vector-borne infectious diseases
- Bird parasitology and diseases
- Viral Infections and Vectors
- interferon and immune responses
- Viral gastroenteritis research and epidemiology
- HIV Research and Treatment
- Parasite Biology and Host Interactions
- Trypanosoma species research and implications
- SARS-CoV-2 detection and testing
- Aquaculture disease management and microbiota
- Hepatitis C virus research
- vaccines and immunoinformatics approaches
- Bacteriophages and microbial interactions
- Influenza Virus Research Studies
- Animal Virus Infections Studies
- Viral Infections and Outbreaks Research
- Bat Biology and Ecology Studies
- Insect symbiosis and bacterial influences
- Malaria Research and Control
- Transgenic Plants and Applications
- Chromatin Remodeling and Cancer
Icahn School of Medicine at Mount Sinai
2020-2024
Mount Sinai Health System
2020-2023
Center for Research and Advanced Studies of the National Polytechnic Institute
2017-2023
University of California, San Francisco
2023
New York Proton Center
2022
University of San Francisco
2022
Instituto Venezolano de Investigaciones Científicas
2012-2021
The emergence of SARS-CoV-2 variants concern suggests viral adaptation to enhance human-to-human transmission
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins interact with the eukaryotic translation machinery, and inhibitors of have potent antiviral effects. We found that drug plitidepsin (aplidin), which has limited clinical approval, possesses activity (90% inhibitory concentration = 0.88 nM) is more than remdesivir against SARS-CoV-2 in vitro by a factor 27.5, toxicity cell culture. Through use drug-resistant mutant, we show mediated through inhibition known target...
Abstract COVID-19 caused by the SARS-CoV-2 virus has become a global pandemic. 3CL protease is virally encoded protein that essential across broad spectrum of coronaviruses with no close human analogs. PF-00835231, inhibitor, exhibited potent in vitro antiviral activity against as single agent. Here we report, design and characterization phosphate prodrug PF-07304814 to enable delivery projected sustained systemic exposure PF-00835231 inhibit coronavirus family selectivity over host targets....
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 from screening in field, we became concerned that phospholipidosis was a shared mechanism underlying antiviral activity of many repurposed drugs. For all 23 cationic amphiphilic tested, including hydroxychloroquine, azithromycin, amiodarone, four others already clinical trials,...
Effective control of COVID-19 requires antivirals directed against SARS-CoV-2. We assessed 10 hepatitis C virus (HCV) protease-inhibitor drugs as potential SARS-CoV-2 antivirals. There is a striking structural similarity the substrate binding clefts main protease (Mpro) and HCV NS3/4A protease. Virtual docking experiments show that these can potentially bind into Mpro substrate-binding cleft. seven inhibit both activity replication in Vero and/or human cells. However, their inhibiting...
Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several variants in preclinical studies. Simultaneously, this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted 10 Spanish hospitals between May and November 2020, 46...
Bats are distinctive among mammals due to their ability fly, use laryngeal echolocation, and tolerate viruses. However, there currently no reliable cellular models for studying bat biology or response viral infections. Here, we created induced pluripotent stem cells (iPSCs) from two species of bats: the wild greater horseshoe (Rhinolophus ferrumequinum) mouse-eared (Myotis myotis). The iPSCs both showed similar characteristics had a gene expression profile resembling that attacked by They...
Abstract Identification of host determinants coronavirus infection informs mechanisms viral pathogenesis and can provide new drug targets. Here we demonstrate that mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) chromatin remodeling complexes, specifically canonical BRG1/BRM-associated factor (cBAF) promote severe acute respiratory syndrome 2 (SARS-CoV-2) represent host-directed therapeutic The catalytic activity SMARCA4 is required for mSWI/SNF-driven accessibility at the ACE2 locus,...
Abstract Variants of SARS-CoV-2 have become a major public health concern due to increased transmissibility, and escape from natural immunity, vaccine protection, monoclonal antibody therapeutics. The highly transmissible Omicron variant has up 32 mutations within the spike protein, many more than previous variants, heightening these concerns immune escape. There are now multiple antiviral therapeutics that received approval for emergency use by FDA target both RNA-dependent RNA polymerase...
Abstract Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in millions of deaths worldwide and massive societal economic burden. Recently, a new variant SARS-CoV-2, known as B.1.1.7, was first detected the United Kingdom is spreading several other countries, heightening public health concern raising questions to resulting effectiveness vaccines therapeutic interventions. We others previously identified host-directed...
Abstract The novel SARS-CoV-2 virus emerged in December 2019 and has few effective treatments. We applied a computational drug repositioning pipeline to differential gene expression signatures derived from publicly available data. utilized three independent published studies acquire or generate lists of differentially expressed genes between control SARS-CoV-2-infected samples. Using rank-based pattern matching strategy based on the Kolmogorov–Smirnov Statistic, were queried against profiles...
Dengue virus (DENV) is a mosquito-borne of the family Flaviviridae The RNA viral genome encodes three structural and seven nonstructural proteins. Nonstructural protein 1 (NS1) multifunctional actively secreted in vertebrate mosquito cells during infection. In cells, NS1 caveolin-1-dependent manner by an unconventional route. caveolin chaperone complex (CCC) cytoplasmic formed caveolin-1 chaperones FKBP52, Cy40, CyA responsible for cholesterol traffic inside cell. this work, we demonstrate...
The death toll and financial stress posed by the recent COVID-19 pandemic have highlighted pressing need to develop safe effective, broad-spectrum inhibitors treat viral infections. To accelerate antiviral drug discovery process, we developed GALILEOTM, a computational platform that interfaces with customizable bioinformatics pipeline geometric deep learning algorithm named ChemPrintTM for in silico screening. Combining these algorithms large chemical repositioning library, discovered...
Parasites can exert selection pressure on their hosts through effects survival, reproductive success, sexually selected ornament, with important ecological and evolutionary consequences, such as changes in population viability. Consequently, hemoparasites have become the focus of recent avian studies. Infection varies significantly among taxa. Various factors might explain differences infection taxa, including habitat, climate, host density, presence vectors, life history immune defence....
There is a pressing need for host-directed therapeutics that elicit broad-spectrum antiviral activities to potentially address current and future viral pandemics. Apratoxin S4 (Apra S4) potent Sec61 inhibitor prevents cotranslational translocation of secretory proteins into the endoplasmic reticulum (ER), leading anticancer antiangiogenic activity both in vitro vivo. Since has been shown be an essential host factor proteostasis, we tested Apra cellular models infection, including SARS-CoV-2,...
ABSTRACT A series of SARS-CoV-2 variants concern (VOCs) have evolved in humans during the COVID-19 pandemic—Alpha, Beta, Gamma, Delta, and Omicron. Here, we used global proteomic genomic analyses infection to understand molecular responses driving VOC evolution. We discovered VOC-specific differences viral RNA protein expression levels, including for N, Orf6, Orf9b, pinpointed several mutations responsible. An analysis host response comprehensive interrogation altered virus-host...
Dengue is the most important mosquito-borne viral disease to humans. virus NS1 a multifunctional protein essential for replication and modulation of innate immunity.
The stress of the Golgi apparatus is an autoregulatory mechanism that induced to compensate for greater demand in functions. No examples responses due physiological stimuli are known. Furthermore, impact on this organelle viral infections occupy vesicular transport during replication unknown. In work, we evaluated if a response triggered dengue and Zika viruses replication, two flaviviruses whose replicative cycle heavily involved with complex, vertebrate mosquito cells. Using GM-130 as...