14 documents found, page 1 of 2
Proximity-Induced Nucleic Acid Degrader (PINAD) approach to targeted RNA degrad...
Mikutis, Sigitas; Rebelo, Maria; Yankova, Eliza; Gu, Muxin; Tang, Cong; Coelho, Ana R; Yang, Mo; Hazemi, Madoka E.; Pires de Miranda, MartaNature has evolved intricate machinery to target and degrade RNA, and some of these molecular mechanisms can be adapted for therapeutic use. Small interfering RNAs and RNase H-inducing oligonucleotides have yielded therapeutic agents against diseases that cannot be tackled using protein-centered approaches. Because these therapeutic agents are nucleic acid-based, they have several inherent drawbacks which inclu...
De novo human angiotensin-converting enzyme 2 decoy NL-CVX1 protects mice from ...
Rebelo, Maria; Tang, Cong; Coelho, Ana R; Labão-Almeida, Carlos; Schneider, Matthias M.; Tatalick, Laurie; Ruivo, Pedro; Pires de Miranda, MartaThe emergence of novel variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need to investigate alternative approaches to prevent infection and treat patients with coronavirus disease 2019. Here, we report the preclinical efficacy of NL-CVX1, a de novo decoy that blocks virus entry into cells by binding with nanomolar affinity and high specificity to the receptor-binding doma...
Endemic SARS-CoV-2 will maintain post-pandemic immunity
Veldhoen, Marc; Simas, J PedroCOVID-19 vaccinations have started. They will stop the pandemic. Citing recent data that are in line with immunological knowledge and predictions, combined with insights of common cold coronaviruses, we here set out the case that the maintenance of population immunity will not depend on continued vaccinations but on the endemic presence of SARS-CoV-2.
A rapid real-time polymerase chain reaction-based live virus microneutralizatio...
Abidi, Syed Hani; Imtiaz, Kehkashan; Kanji, Akbar; Qaiser, Shama; Khan, Erum; Iqbal, Kiran; Veldhoen, Marc; Ghias, Kulsoom; Simas, J Pedro; Hasan, ZahraBackground: Individuals recovering from COVID-19 are known to have antibodies against the Spike and other structural proteins. Antibodies against Spike have been shown to display viral neutralization. However, not all antibodies against Spike have neutralizing ability although they may be cross-reactive. There is a need for easy-to-use SARS-CoV-2 neutralizing assays for the determination of virus-neutralizing a...
Seroprevalence of anti‐SARS‐CoV‐2 antibodies in COVID‐19 patients and healthy v...
Figueiredo-Campos, Patricia; Blankenhaus, Birte; Mota, Catarina; Gomes, Andreia; Serrano, Marta; Ariotti, Silvia; Costa, Catarina; Nunes-Cabaço, HelenaSARS-CoV-2 has emerged as a human pathogen, causing clinical signs, from fever to pneumonia-COVID-19-but may remain mild or asymptomatic. To understand the continuing spread of the virus, to detect those who are and were infected, and to follow the immune response longitudinally, reliable and robust assays for SARS-CoV-2 detection and immunological monitoring are needed. We quantified IgM, IgG, and IgA antibodi...
Cross-species conservation of episome maintenance provides a basis for in vivo ...
Habison, Aline C.; Pires de Miranda, Marta; Beauchemin, Chantal; Tan, Min; A. Cerqueira, Sofia; Correia, Bruno; Ponnusamy, Rajesh; Usherwood, Edward J.Many pathogens, including Kaposi's sarcoma herpesvirus (KSHV), lack tractable small animal models. KSHV persists as a multi-copy, nuclear episome in latently infected cells. KSHV latency-associated nuclear antigen (kLANA) binds viral terminal repeat (kTR) DNA to mediate episome persistence. Model pathogen murine gammaherpesvirus 68 (MHV68) mLANA acts analogously on mTR DNA. kLANA and mLANA differ substantially ...
KSHV but not MHV-68 LANA induces a strong bend upon binding to terminal repeat ...
Ponnusamy, Rajesh; Petoukhov, Maxim V.; Correia, Bruno; Custodio, Tania F.; Juillard, Franceline; Tan, Min; Pires de Miranda, Marta; Carrondo, Maria A.Latency-associated nuclear antigen (LANA) is central to episomal tethering, replication and transcriptional regulation of γ2-herpesviruses. LANA binds cooperatively to the terminal repeat (TR) region of the viral episome via adjacent LANA binding sites (LBS), but the molecular mechanism by which LANA assembles on the TR remains elusive. We show that KSHV LANA and MHV-68 LANA proteins bind LBS DNA using striking...
Murid Gammaherpesvirus latency-associated protein M2 promotes the formation of ...
Fontinha, Diana; Lopes, Filipa B.; Marques, Sofia; Simas, J PedroEstablishment of persistent infection in memory B cells by murid herpesvirus-4 (MuHV-4) depends on the proliferation of latently infected germinal center B cells, for which T cell help is essential. Whether the virus is capable of modulating B-T helper cell interaction for its own benefit is still unknown. Here, we investigate if the MuHV-4 latency associated M2 protein, which assembles multiprotein complexes w...
The Kaposi Sarcoma Herpesvirus latency-associated nuclear antigen DNA binding d...
Li, Shijun; Tan, Min; Juillard, Franceline; Ponnusamy, Rajesh; Correia, Bruno; Simas, J Pedro; Carrondo, Maria A.; McVey, Colin E.; Kaye, Kenneth M.Kaposi sarcoma-associated herpesvirus (KSHV) has a causative role in several human malignancies. KSHV latency-associated nuclear antigen (LANA) mediates persistence of viral episomes in latently infected cells. LANA mediates KSHV DNA replication and segregates episomes to progeny nuclei. The structure of the LANA DNA binding domain was recently solved, revealing a positive electrostatic patch opposite the DNA b...
Establishment of Murine Gammaherpesvirus latency in B cells is not a stochastic...
Decalf, Jérémie; Godinho-Silva, Cristina; Fontinha, Diana; Marques, Sofia; Simas, J PedroMurid γ-herpesvirus-4 (MuHV-4) promotes polyclonal B cell activation and establishes latency in memory B cells via unclear mechanisms. We aimed at exploring whether B cell receptor specificity plays a role in B cell susceptibility to viral latency and how this is related to B cell activation. We first observed that MuHV-4-specific B cells represent a minority of the latent population, and to better understand t...