Rana Abdelnabi
A5064479176- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Mosquito-borne diseases and control
- Viral gastroenteritis research and epidemiology
- Viral Infections and Immunology Research
- Respiratory viral infections research
- HIV Research and Treatment
- Animal Virus Infections Studies
- Viral Infections and Vectors
- SARS-CoV-2 detection and testing
- vaccines and immunoinformatics approaches
- interferon and immune responses
- Monoclonal and Polyclonal Antibodies Research
- Viral Infections and Outbreaks Research
- Influenza Virus Research Studies
- RNA and protein synthesis mechanisms
- Insect symbiosis and bacterial influences
- HIV/AIDS drug development and treatment
- Malaria Research and Control
- Virus-based gene therapy research
- Virology and Viral Diseases
- Pneumocystis jirovecii pneumonia detection and treatment
- Computational Drug Discovery Methods
- Bacteriophages and microbial interactions
- Studies on Chitinases and Chitosanases
KU Leuven
2016-2025
Rega Institute for Medical Research
2016-2025
Global Virus Network
2021-2022
University of Salerno
2016
Efficient therapeutic options are needed to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has caused more than 922,000 fatalities as 13 September 2020. We report isolation and characterization two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 S2M11) protect hamsters against challenge. Cryo-electron microscopy structures show S2E12 S2M11 competitively block angiotensin-converting enzyme (ACE2) attachment also locks spike in a closed...
An ideal therapeutic anti-SARS-CoV-2 antibody would resist viral escape
Targeting a range of betacoranaviruses In the past 20 years, three highly pathogenic β-coronaviruses have crossed from animals to humans, including most recent: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A spike protein that decorates these viruses has an S1 domain binds host cell receptors and S2 fuses viral membranes allow entry. The is target many neutralizing antibodies but more genetically variable than S2, can exert selective pressure, leading resistant variants....
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread around the globe after its emergence in Wuhan December 2019. With no specific therapeutic and prophylactic options available, virus has infected millions of people which more than half a million succumbed to viral disease, COVID-19. The urgent need for an effective treatment together with lack small animal infection models led clinical trials using repurposed drugs without preclinical evidence their vivo efficacy. We...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages carry distinct spike mutations resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity vaccine boosters elicit plasma-neutralizing against BA.1, BA.2, BA.2.12.1, and BA.4/5, breakthrough infections, but not vaccination alone, induce neutralizing the nasal mucosa. Consistent with immunological imprinting, most derived memory B cells plasma of cases...
The coronavirus spike glycoprotein attaches to host receptors and mediates viral fusion. Using a broad screening approach, we isolated seven monoclonal antibodies (mAbs) that bind all human-infecting proteins from severe acute respiratory syndrome 2 (SARS-CoV-2) immune donors. These mAbs recognize the fusion peptide acquire affinity breadth through somatic mutations. Despite targeting conserved motif, only some show neutralizing activity in vitro against alpha- betacoronaviruses, including...
Understanding broadly neutralizing sarbecovirus antibody responses is key to developing countermeasures against SARS-CoV-2 variants and future zoonotic sarbecoviruses. We describe the isolation characterization of a human monoclonal antibody, designated S2K146, that neutralizes viruses belonging SARS-CoV- SARS-CoV-2-related clades which use ACE2 as an entry receptor. Structural functional studies show most virus residues directly bind S2K146 are also involved in binding ACE2. This allows...
Favipiravir and Molnupiravir, orally available antivirals, have been reported to exert antiviral activity against SARS-CoV-2. First efficacy data recently in COVID-19 patients.We here report on the combined effect of both drugs a SARS-CoV-2 Syrian hamster infection model. The infected hamsters were treated twice daily with vehicle (the control group) or suboptimal dose each compound combination compounds.When animals doses Molnupiravir at time infection, marked potency endpoint is observed....
Abstract The emergence of SARS-CoV-2 variants concern (VoCs) has exacerbated the COVID-19 pandemic. Currently available monoclonal antibodies and vaccines appear to have reduced efficacy against some these VoCs. Antivirals targeting conserved proteins are unlikely be affected by mutations arising in VoCs should therefore effective emerging variants. We here investigate molnupiravir, currently phase 2 clinical trials, hamsters infected with Wuhan strain or B.1.1.7 B.1.351 Molnupiravir proved...
Within one year after its emergence, more than 108 million people acquired SARS-CoV-2 and almost 2·4 succumbed to COVID-19. New variants of concern (VoC) are emerging all over the world, with threat being readily transmitted, virulent, or escaping naturally vaccine-induced immunity. At least three major prototypic VoC have been identified, i.e. United Kingdom, UK (B.1.1.7), South African (B.1.351) Brazilian (B.1.1.28.1) variants. These replacing formerly dominant strains sparking new...
Abstract There is an urgent need for potent and selective antivirals against SARS-CoV-2. Pfizer developed PF-07321332 (PF-332), a inhibitor of the viral main protease (Mpro, 3CLpro) that can be dosed orally in clinical development. We here report PF-332 exerts equipotent vitro activity four SARS-CoV-2 variants concerns (VoC) it completely arrest replication alpha variant primary human airway epithelial cells grown at air-liquid interface. Treatment Syrian Golden hamsters with (250 mg/kg,...
The emergence of SARS-CoV-2 variants concern (VoCs) has exacerbated the COVID-19 pandemic. End November 2021, a new variant namely omicron (B.1.1.529) emerged. Since this is heavily mutated in spike protein, WHO classified as 5th (VoC). We previously demonstrated that ancestral strain and other VoCs replicate efficiently cause COVID19-like pathology Syrian hamsters. here wanted to explore infectivity comparison D614G hamster model. Strikingly, hamsters had been infected with variant, 3 log
SARS-CoV-2 entry into host cells is orchestrated by the spike (S) glycoprotein that contains an immunodominant receptor-binding domain (RBD) targeted largest fraction of neutralizing antibodies (Abs) in COVID-19 patient plasma. Little known about Abs binding to epitopes outside RBD and their contribution protection. Here, we describe 41 human monoclonal (mAbs) derived from memory B cells, which recognize S N-terminal (NTD) show a subset them neutralize ultrapotently. We define antigenic map...
Self-amplifying RNA vaccines may induce equivalent or more potent immune responses at lower doses compared to non-replicating mRNA via amplified antigen expression. In this paper, we demonstrate that 1 μg of an LNP-formulated dual-antigen self-amplifying vaccine (ZIP1642), encoding both the S-RBD and N antigen, elicits considerably higher neutralizing antibody titers against Wuhan-like Beta B.1.351 Delta B.1.617.2 SARS-CoV-2 variants those convalescent patients. addition, ZIP1642 vaccination...
Abstract The SARS-CoV-2 Omicron variant has very high levels of transmission, is resistant to neutralization by authorized therapeutic human monoclonal antibodies (mAb) and less sensitive vaccine-mediated immunity. To provide additional therapies against Omicron, we isolated a mAb named P2G3 from previously infected vaccinated donor showed that it picomolar-range neutralizing activity BA.1, BA.1.1, BA.2 all other variants tested. We solved the structure Fab in complex with spike using...
Abstract The membrane (M) protein of betacoronaviruses is well conserved and has a key role in viral assembly 1,2 . Here we describe the identification JNJ-9676, small-molecule inhibitor targeting coronavirus M protein. JNJ-9676 demonstrates vitro nanomolar antiviral activity against SARS-CoV-2, SARS-CoV sarbecovirus strains from bat pangolin zoonotic origin. Using cryogenic electron microscopy (cryo-EM), determined binding pocket formed by transmembrane domains dimer. Compound stabilized...
Favipiravir (T-705) is a broad-spectrum antiviral agent that has been approved in Japan for the treatment of influenza virus infections. T-705 also inhibits replication various RNA viruses, including chikungunya (CHIKV). We demonstrated earlier K291R mutation F1 motif RNA-dependent polymerase (RdRp) CHIKV responsible low-level resistance to T-705. Interestingly, this lysine highly conserved RdRp positive-sense single-stranded (+ssRNA) viruses. To obtain insights into unique activity T-705,...
Broadly neutralizing antibodies are an important treatment for individuals with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2). Antibody-based therapeutics also essential pandemic preparedness against future Sarbecovirus outbreaks. Camelid-derived single domain (VHHs) exhibit potent antimicrobial activity and being developed as SARS-CoV-2–neutralizing antibody-like therapeutics. Here, we identified VHHs that neutralize both SARS-CoV-1...
Control of the ongoing SARS-CoV-2 pandemic is endangered by emergence viral variants with increased transmission efficiency, resistance to marketed therapeutic antibodies, and reduced sensitivity vaccine-induced immunity. Here, we screen B cells from COVID-19 donors identify P5C3, a highly potent broadly neutralizing monoclonal antibody picomolar activity against all concern (VOCs) identified date. Structural characterization P5C3 Fab in complex spike demonstrates defined large buried...
SARS-CoV-2 Omicron sublineages carry distinct spike mutations and represent an antigenic shift resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity vaccine boosters result potent plasma neutralizing activity against BA.1 BA.2 breakthrough infections, but not vaccination-only, induce the nasal mucosa. Consistent with immunological imprinting, most derived memory B cells of cases cross-react Wuhan-Hu-1, receptor-binding domains whereas...