As of August 16,2021,there have been 207,173,086 confirmed cases and 4,361,996 deaths due to the coronavirus disease(COVID-19),and the pandemic remains a global challenge.To date,no effective and approved drugs are av...As of August 16,2021,there have been 207,173,086 confirmed cases and 4,361,996 deaths due to the coronavirus disease(COVID-19),and the pandemic remains a global challenge.To date,no effective and approved drugs are available for the treatment of COVID-19.Angiotensin-converting enzyme 2(ACE2)plays a crucial role in the invasion into host cells by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the etiological agent of COVID-19.Notably,ACE2 density is influenced by medical conditions,such as hypertension,or by drugs,including angiotensin-converting enzyme inhibitors(ACEIs)and angiotensin receptor blockers(ARBs),which can change the fate of SARS-CoV-2 infectivity.ACE2 is a target for these drugs and can be manipulated to limit the viral entry and replication within the cells.Different strategies aimed at blocking ACE2 with small molecules,peptides,and antibodies,or by neutralizing the virus through its competitive binding with human recombinant soluble ACE2(hrsACE2)are currently under investigation.In this article,we review the current state of knowledge that emphasizes the need to find effective therapeutic agents against COVID-19 by exploiting ACE2 as a potential target.The increased soluble ACE2 levels and the application of hrsACE2 in patients with COVID-19 can be implemented to control the disease.It has not yet been established whether hypertension and other comorbidities,independent of age,have a direct role in COVID-19.Therefore,the use of renin-angiotensin system inhibitors,ACEIs and ARBs,should not be discontinued during COVID-19 treatment.展开更多
The growth of COVID-19 pandemic throughout more than 213 countries around the world have put a lot of pressures on governments and health services to try to stop the rapid expansion of the pandemic.During 2009,H1N1 In...The growth of COVID-19 pandemic throughout more than 213 countries around the world have put a lot of pressures on governments and health services to try to stop the rapid expansion of the pandemic.During 2009,H1N1 Influenza pandemic,statistical and mathematical methods were used to track how the virus spreads around countries.Most of these models that were developed at the beginning of the XXI century are based on the classical susceptible-infected-recovered(SIR)model developed almost a hundred years ago.The evolution of this model allows us to forecast and compute basic and effective reproduction numbers(R_(t) and R_(0)),measures that quantify the epidemic potential of a pathogen and estimates different scenarios.In this study,we present a traditional estimation technique for R_(0) with statistical distributions by best fitting and a Bayesian approach based on continuous feed of prior distributions to obtain posterior distributions and computing real time R_(t).We use data from COVID-19 officially reported cases in Ecuador since the first confirmed case on February 29th.Because of the lack of data,in the case of R_(0) we compare two methods for the estimation of these parameters below exponential growth and maximum likelihood estimation.We do not make any assumption about the evolution of cases due to limited information and we use previous methods to compare scenarios about R_(0) and in the case of R_(t) we used Bayesian inference to model uncertainty in contagious proposing a new modification to the well-known model of Bettencourt and Ribeiro based on a time window of m days to improve estimations.Ecuadorian R_(0) with exponential growth criteria was 3.45 and with the maximum likelihood estimation method was 2.93.The results show that Guayas,Pichincha and Manabíwere the provinces with the highest number of cases due to COVID-19.Some reasons explain the increased transmissibility in these localities:massive events,population density,cities dispersion patterns,and the delayed time of public health actions to contain pandemic.In conclusion,this is a novel approach that allow us to measure infection dynamics and outbreak distribution when not enough detailed data is available.The use of this model can be used to predict pandemic distribution and to implement data-based effective measures.展开更多
To assess the impact of the key non-synonymous amino acid substitutions in the RBD of the spike protein of SARS-CoV-2 variant B.1.617.1(dominant variant identified in the current India outbreak)on the infectivity and ...To assess the impact of the key non-synonymous amino acid substitutions in the RBD of the spike protein of SARS-CoV-2 variant B.1.617.1(dominant variant identified in the current India outbreak)on the infectivity and neutralization activities of the immune sera,L452R and E484Q(L452R-E484Q variant),pseudotyped virus was constructed(with the D614G background).The impact on binding with the neutralizing antibodies was also assessed with an ELISA assay.Pseudotyped virus carrying a L452R-E484Q variant showed a comparable infectivity compared with D614G.However,there was a significant reduction in the neutralization activity of the immune sera from non-human primates vaccinated with a recombinant receptor binding domain(RBD)protein,convalescent patients,and healthy vaccinees vaccinated with anmRNA vaccine.In addition,there was a reduction in binding of L452R-E484Q-D614G protein to the antibodies of theimmune sera fromvaccinated nonhuman primates.These results highlight the interplay between infectivity and other biologic factors involved in the natural evolution of SARS-CoV-2.Reduced neutralization activities against the L452R-E484Q variant will have an impact on health authority planning and implications for the vaccination strategy/newvaccine development.展开更多
文摘As of August 16,2021,there have been 207,173,086 confirmed cases and 4,361,996 deaths due to the coronavirus disease(COVID-19),and the pandemic remains a global challenge.To date,no effective and approved drugs are available for the treatment of COVID-19.Angiotensin-converting enzyme 2(ACE2)plays a crucial role in the invasion into host cells by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the etiological agent of COVID-19.Notably,ACE2 density is influenced by medical conditions,such as hypertension,or by drugs,including angiotensin-converting enzyme inhibitors(ACEIs)and angiotensin receptor blockers(ARBs),which can change the fate of SARS-CoV-2 infectivity.ACE2 is a target for these drugs and can be manipulated to limit the viral entry and replication within the cells.Different strategies aimed at blocking ACE2 with small molecules,peptides,and antibodies,or by neutralizing the virus through its competitive binding with human recombinant soluble ACE2(hrsACE2)are currently under investigation.In this article,we review the current state of knowledge that emphasizes the need to find effective therapeutic agents against COVID-19 by exploiting ACE2 as a potential target.The increased soluble ACE2 levels and the application of hrsACE2 in patients with COVID-19 can be implemented to control the disease.It has not yet been established whether hypertension and other comorbidities,independent of age,have a direct role in COVID-19.Therefore,the use of renin-angiotensin system inhibitors,ACEIs and ARBs,should not be discontinued during COVID-19 treatment.
基金The author(s)disclosed receipt the financial support for the research and publication of this article from Universidad de Las Americas through their annual general research projects funds.
文摘The growth of COVID-19 pandemic throughout more than 213 countries around the world have put a lot of pressures on governments and health services to try to stop the rapid expansion of the pandemic.During 2009,H1N1 Influenza pandemic,statistical and mathematical methods were used to track how the virus spreads around countries.Most of these models that were developed at the beginning of the XXI century are based on the classical susceptible-infected-recovered(SIR)model developed almost a hundred years ago.The evolution of this model allows us to forecast and compute basic and effective reproduction numbers(R_(t) and R_(0)),measures that quantify the epidemic potential of a pathogen and estimates different scenarios.In this study,we present a traditional estimation technique for R_(0) with statistical distributions by best fitting and a Bayesian approach based on continuous feed of prior distributions to obtain posterior distributions and computing real time R_(t).We use data from COVID-19 officially reported cases in Ecuador since the first confirmed case on February 29th.Because of the lack of data,in the case of R_(0) we compare two methods for the estimation of these parameters below exponential growth and maximum likelihood estimation.We do not make any assumption about the evolution of cases due to limited information and we use previous methods to compare scenarios about R_(0) and in the case of R_(t) we used Bayesian inference to model uncertainty in contagious proposing a new modification to the well-known model of Bettencourt and Ribeiro based on a time window of m days to improve estimations.Ecuadorian R_(0) with exponential growth criteria was 3.45 and with the maximum likelihood estimation method was 2.93.The results show that Guayas,Pichincha and Manabíwere the provinces with the highest number of cases due to COVID-19.Some reasons explain the increased transmissibility in these localities:massive events,population density,cities dispersion patterns,and the delayed time of public health actions to contain pandemic.In conclusion,this is a novel approach that allow us to measure infection dynamics and outbreak distribution when not enough detailed data is available.The use of this model can be used to predict pandemic distribution and to implement data-based effective measures.
文摘To assess the impact of the key non-synonymous amino acid substitutions in the RBD of the spike protein of SARS-CoV-2 variant B.1.617.1(dominant variant identified in the current India outbreak)on the infectivity and neutralization activities of the immune sera,L452R and E484Q(L452R-E484Q variant),pseudotyped virus was constructed(with the D614G background).The impact on binding with the neutralizing antibodies was also assessed with an ELISA assay.Pseudotyped virus carrying a L452R-E484Q variant showed a comparable infectivity compared with D614G.However,there was a significant reduction in the neutralization activity of the immune sera from non-human primates vaccinated with a recombinant receptor binding domain(RBD)protein,convalescent patients,and healthy vaccinees vaccinated with anmRNA vaccine.In addition,there was a reduction in binding of L452R-E484Q-D614G protein to the antibodies of theimmune sera fromvaccinated nonhuman primates.These results highlight the interplay between infectivity and other biologic factors involved in the natural evolution of SARS-CoV-2.Reduced neutralization activities against the L452R-E484Q variant will have an impact on health authority planning and implications for the vaccination strategy/newvaccine development.
