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1.
Microbiology Research ; 12(3):727, 2021.
Article in English | ProQuest Central | ID: covidwho-1834839

ABSTRACT

Zika virus (ZIKV) is a mosquito-borne flavivirus in which human infection became relevant during recent outbreaks in Latin America due to its unrecognized association with fetal neurological disorders. Currently, there are no approved effective antivirals or vaccines for the treatment or prevention of ZIKV infections. Amantadine and rimantadine are approved antivirals used against susceptible influenza A virus infections that have been shown to have antiviral activity against other viruses, such as dengue virus (DENV). Here, we report the in vitro effectiveness of both amantadine and rimantadine hydrochlorides against ZIKV replication, resulting in a dose-dependent reduction in viral titers of a ZIKV clinical isolate and two different ZIKV reference strains. Additionally, we demonstrate similar in vitro antiviral activity of these drugs against DENV-1 and yellow fever virus (YFV), although at higher drug concentrations for the latter. ZIKV replication was inhibited at drug concentrations well below cytotoxic levels of both compounds, as denoted by the high selectivity indexes obtained with the tested strains. Further work is absolutely needed to determine the potential clinical use of these antivirals against ZIKV infections, but our results suggest the existence of a highly conserved mechanism across flavivirus, susceptible to be blocked by modified more specific adamantane compounds.

2.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-295526

ABSTRACT

SARS-CoV-2 variants of concern (VoC) show reduced neutralization by vaccine-induced and therapeutic monoclonal antibodies. We tested therapeutic equine polyclonal antibodies (pAbs) against four VoC (alpha, beta, epsilon and gamma). We show that equine pAbs efficiently neutralize VoC, suggesting they are an effective, broad coverage, low-cost and a scalable COVID-19 treatment.

4.
Front Med (Lausanne) ; 8: 735853, 2021.
Article in English | MEDLINE | ID: covidwho-1436006

ABSTRACT

SARS-CoV-2 variants of concern show reduced neutralization by vaccine-induced and therapeutic monoclonal antibodies; therefore, treatment alternatives are needed. We tested therapeutic equine polyclonal antibodies (pAbs) that are being assessed in clinical trials in Costa Rica against five globally circulating variants of concern: alpha, beta, epsilon, gamma and delta, using plaque reduction neutralization assays. We show that equine pAbs efficiently neutralize the variants of concern, with inhibitory concentrations in the range of 0.146-1.078 µg/mL, which correspond to extremely low concentrations when compared to pAbs doses used in clinical trials. Equine pAbs are an effective, broad coverage, low-cost and a scalable COVID-19 treatment.

5.
Emerg Infect Dis ; 27(7): 1811-1820, 2021 07.
Article in English | MEDLINE | ID: covidwho-1278358

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, and the number of worldwide cases continues to rise. The zoonotic origins of SARS-CoV-2 and its intermediate and potential spillback host reservoirs, besides humans, remain largely unknown. Because of ethical and experimental constraints and more important, to reduce and refine animal experimentation, we used our repository of well-differentiated airway epithelial cell (AEC) cultures from various domesticated and wildlife animal species to assess their susceptibility to SARS-CoV-2. We observed that SARS-CoV-2 replicated efficiently only in monkey and cat AEC culture models. Whole-genome sequencing of progeny viruses revealed no obvious signs of nucleotide transitions required for SARS-CoV-2 to productively infect monkey and cat AEC cultures. Our findings, together with previous reports of human-to-animal spillover events, warrant close surveillance to determine the potential role of cats, monkeys, and closely related species as spillback reservoirs for SARS-CoV-2.


Subject(s)
Animals, Wild , COVID-19 , Animals , Epithelial Cells , Humans , Respiratory System , SARS-CoV-2
6.
Sci Rep ; 11(1): 9825, 2021 05 10.
Article in English | MEDLINE | ID: covidwho-1223113

ABSTRACT

In the current global emergency due to SARS-CoV-2 outbreak, passive immunotherapy emerges as a promising treatment for COVID-19. Among animal-derived products, equine formulations are still the cornerstone therapy for treating envenomations due to animal bites and stings. Therefore, drawing upon decades of experience in manufacturing snake antivenom, we developed and preclinically evaluated two anti-SARS-CoV-2 polyclonal equine formulations as potential alternative therapy for COVID-19. We immunized two groups of horses with either S1 (anti-S1) or a mixture of S1, N, and SEM mosaic (anti-Mix) viral recombinant proteins. Horses reached a maximum anti-viral antibody level at 7 weeks following priming, and showed no major adverse acute or chronic clinical alterations. Two whole-IgG formulations were prepared via hyperimmune plasma precipitation with caprylic acid and then formulated for parenteral use. Both preparations had similar physicochemical and microbiological quality and showed ELISA immunoreactivity towards S1 protein and the receptor binding domain (RBD). The anti-Mix formulation also presented immunoreactivity against N protein. Due to high anti-S1 and anti-RBD antibody content, final products exhibited high in vitro neutralizing capacity of SARS-CoV-2 infection, 80 times higher than a pool of human convalescent plasma. Pre-clinical quality profiles were similar among both products, but clinical efficacy and safety must be tested in clinical trials. The technological strategy we describe here can be adapted by other producers, particularly in low- and middle-income countries.


Subject(s)
COVID-19/immunology , COVID-19/therapy , Coronavirus Nucleocapsid Proteins/immunology , Horses/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/virology , Coronavirus Nucleocapsid Proteins/genetics , Coronavirus Nucleocapsid Proteins/metabolism , Enzyme-Linked Immunosorbent Assay , Humans , Immunization/methods , Immunization, Passive/methods , Immunoglobulin G/immunology , Recombinant Proteins/immunology , Recombinant Proteins/metabolism , SARS-CoV-2/metabolism , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
7.
Front Res Metr Anal ; 6: 664880, 2021.
Article in English | MEDLINE | ID: covidwho-1207798

ABSTRACT

Science diplomacy is a fast-growing field of research, policy, and practice dedicated to understanding and reinforcing the connections between science and international affairs to tackle national, regional, and global issues. By aligning science and diplomacy, countries can attract talent, strengthen their national research ecosystems, provide avenues for participation of scientists in policy, and coordinate integrated solutions to challenges with technical dimensions. While Latin America has a long tradition of bilateral and regional cooperation, science still plays a marginal role in foreign policy, as has become evidenced by the response to the COVID-19 pandemic. With few exceptions, Latin American nations have a relatively immature science, technology, and innovation ecosystem, compounded by low public and private investments in research, coexisting with profound socio-economic inequalities, and large vulnerable populations. Such challenging conditions have created barriers to a fluid relationship between science and diplomacy, fundamentally characterized by inefficient communication between scientists and policymakers, weak collaboration channels, and duplicated roles, which altogether perpetuate siloed mentalities and a lack of trust between the two communities. Over the last decade, a first influential wave of Latin American scientists, diplomats, and other professionals, including five of the co-authors, have undertaken science diplomacy training provided by specialized organizations. Through these experiences, we recognized the need to elevate awareness and build capacities in science diplomacy in our respective countries and overall, across Latin America. Here, we describe emerging efforts and mechanisms to bridge the gap between scientists and policymakers at the national and regional level. Furthermore, we offer recommendations to amplify the impact of those pioneering initiatives toward consolidating a robust science diplomacy practice across the region. The national experiences described from Costa Rica, Mexico, and Panama can serve as a roadmap for other Latin American nations in the early process of developing a science diplomacy strategy, so they can also align themselves to a collective pathway. Most critically, we propose a way forward so that Latin America can leapfrog beyond disjointed training of individuals into integrated institutional strategies that can harness the tools of science diplomacy to enhance science-informed multilateral cooperation and enable more effective science-informed policymaking.

8.
Infect Genet Evol ; 92: 104872, 2021 08.
Article in English | MEDLINE | ID: covidwho-1202173

ABSTRACT

Genome sequencing is a key strategy in the surveillance of SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Latin America is the hardest-hit region of the world, accumulating almost 20% of COVID-19 cases worldwide. In Costa Rica, from the first detected case on March 6th to December 31st almost 170,000 cases have been reported. We analyzed the genomic variability during the SARS-CoV-2 pandemic in Costa Rica using 185 sequences, 52 from the first months of the pandemic, and 133 from the current wave. Three GISAID clades (G, GH, and GR) and three PANGOLIN lineages (B.1, B.1.1, and B.1.291) were predominant, suggesting multiple re-introductions from other regions. The whole-genome variant calling analysis identified a total of 283 distinct nucleotide variants, following a power-law distribution with 190 single nucleotide mutations in a single sequence, and only 16 mutations were found in >5% sequences. These mutations were distributed through the whole genome. The prevalence of worldwide-found variant D614G in the Spike (98.9% in Costa Rica), ORF8 L84S (1.1%) is similar to what is found elsewhere. Interestingly, the frequency of mutation T1117I in the Spike has increased during the current pandemic wave beginning in May 2020 in Costa Rica, reaching 29.2% detection in the full genome analyses in November 2020. This variant has been observed in less than 1% of the GISAID reported sequences worldwide in 2020. Structural modeling of the Spike protein with the T1117I mutation suggests a potential effect on the viral oligomerization needed for cell infection, but no differences with other genomes on transmissibility, severity nor vaccine effectiveness are predicted. In conclusion, genome analyses of the SARS-CoV-2 sequences over the course of the COVID-19 pandemic in Costa Rica suggest the introduction of lineages from other countries and the detection of mutations in line with other studies, but pointing out the local increase in the detection of Spike-T1117I variant. The genomic features of this virus need to be monitored and studied in further analyses as part of the surveillance program during the pandemic.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Genetic Variation , Genomics , SARS-CoV-2/genetics , Costa Rica/epidemiology , Female , Humans , Male , Models, Molecular , Mutation , Phylogeny , Population Surveillance , Protein Conformation , Spike Glycoprotein, Coronavirus/genetics
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