Antiviral Screening
RESEARCH PLATFORMS
The CNB Antiviral Discovery and Characterization Platform is devoted to the identification of antiviral compounds against human pathogenic viruses of biomedical relevance using unbiased phenotypic cell culture screening systems which serve as models for viral infections including: SARS-CoV-2, MERS, dengue, West Nile, hepatitis B and C viruses as well as influenza A virus. Simultaneous monitorization of viral propagation efficiency and compound cytotoxicity enables identification of non-toxic, effective antiviral molecules.
Example of virus-infected cultures treated with solvent (left panel) or treated with an experimental antiviral, showing a strong reduction in viral infection efficiency (viral antigen, green; cell nuclei, blue).
Scheme of the platform workflow.
Given the unbiased nature of the screening methodology, our studies evaluate both virus and host-targeted antiviral molecules, increasing the success rate, given the large number of potential targets. The downside of the methodology is that the molecular target of the identified compound is unknown a priori, and a complex target deconvolution process needs to be implemented to define the mode of action of the candidates.
Our platform has implemented a number of surrogate systems and approaches to define the mode of action of candidate antivirals. These include unbiased techniques such as chemical proteomics, in collaboration with the CNB Proteomics Core, as well as directed evolution and reverse genetics studies to define genetic resistance profiles to the candidate compounds.
The platform has extensively collaborated with Academic Institutions (see Publications) which provided the candidate compounds. Our platform is also part of a European Consortium for the Identification of Antiviral Molecules.
Equipment
– Access to BSL2 and BSL3 cell culture facilities under the Biosafety Service Supervision.
– Automated liquid handler for cell culture 96-well plates
– Tecan Spark Cyto Multimodal Analysis device for automated fluorescence microscopy, luminometry, fluorimetry and colorimetry analyses.
– Real-time qPCR device
– Fully equipped molecular virology laboratories (Gastaminza and Garaigorta laboratories).
Publicaciones
Fernández-Soto D, Bueno P, Garaigorta U, Gastaminza P, Bueno JL, Duarte RF, Jara R, Valés-Gómez M, Reyburn HT. SARS-CoV-2 membrane protein-specific antibodies from critically ill SARS-CoV-2-infected individuals interact with Fc receptor-expressing cells but do not neutralize the virus. J Leukoc Biol. 2024 Apr 29;115(5):985-991. doi: 10.1093/jleuko/qiae017.
Fàbrega-Ferrer M, Herrera-Morandé A, Muriel-Goñi S, Pérez-Saavedra J, BuenoP, Castro V, Garaigorta U, Gastaminza P, Coll M. Structure and inhibition of SARS-CoV-1 and SARS-CoV-2 main proteases by oral antiviral compound AG7404. Antiviral Res. 2022 Dec;208:105458. doi: 10.1016/j.antiviral.2022.105458. Epub 2022 Nov 3.
Casasnovas JM, Margolles Y, Noriega MA, Guzmán M, Arranz R, Melero R, Casanova M, Corbera JA, Jiménez-de-Oya N, Gastaminza P, Garaigorta U, Saiz JC, Martín-Acebes MÁ, Fernández LÁ. Nanobodies Protecting From Lethal SARS-CoV-2 Infection Target Receptor Binding Epitopes Preserved in Virus Variants Other Than Omicron. Front Immunol. 2022 Apr 25;13:863831. doi: 10.3389/fimmu.2022.863831.
Oliva MÁ, Tosat-Bitrián C, Barrado-Gil L, Bonato F, Galindo I, Garaigorta U, Álvarez-Bernad B, París-Ogáyar R, Lucena-Agell D, Giménez-Abián JF, García-Dorival I, Urquiza J, Gastaminza P, Díaz JF, Palomo V, Alonso C. Effect of Clinically Used Microtubule Targeting Drugs on Viral Infection and Transport Function. Int J Mol Sci. 2022 Mar 22;23(7):3448. doi: 10.3390/ijms23073448.
Jimenez-Aleman GH, Castro V, Londaitsbehere A, Gutierrez-Rodríguez M, Garaigorta U, Solano R, Gastaminza P. SARS-CoV-2 Fears Green: The Chlorophyll Catabolite Pheophorbide A Is a Potent Antiviral. Pharmaceuticals (Basel). 2021 Oct 15;14(10):1048. doi: 10.3390/ph14101048.
Ginex T, Garaigorta U, Ramírez D, Castro V, Nozal V, Maestro I, García-Cárceles J, Campillo NE, Martinez A, Gastaminza P, Gil C. Host-Directed FDA-Approved Drugs with Antiviral Activity against SARS-CoV-2 Identified by Hierarchical In Silico/In Vitro Screening Methods. Pharmaceuticals (Basel). 2021 Apr 6;14(4):332. doi: 10.3390/ph14040332.
Personnel
Scientific Coordinators
Urtzi Garaigorta
Pablo Gastaminza
Lab assistants
Jennifer Moya Vaquero
Laura Barbado Fernández
PhD candidate
Paula Bueno Fernández
