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Made available in DSpace on 2022-04-28T19:44:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-01 Agencia Nacional de Investigación e Innovación Comisión Sectorial de Investigación Científica Fondo Nacional de Desarrollo Científico y Tecnológico The molecular evolution of life on earth along with changing environmental, conditions has rendered mankind susceptible to endemic and pandemic emerging infectious diseases. The effects of certain systemic viral and bacterial infections on morbidity and mortality are considered as examples of recent emerging infections. Here we will focus on three examples of infections that are important in pregnancy and early childhood: SARS-CoV-2 virus, Zika virus, and Mycoplasma species. The basic structural characteristics of these infectious agents will be examined, along with their general pathogenic mechanisms. Coronavirus infections, such as caused by the SARS-CoV-2 virus, likely evolved from zoonotic bat viruses to infect humans and cause a pandemic that has been the biggest challenge for humanity since the Spanish Flu pandemic of the early 20th century. In contrast, Zika Virus infections represent an expanding infectious threat in the context of global climate change. The relationship of these infections to pregnancy, the vertical transmission and neurological sequels make these viruses highly relevant to the topics of this special issue. Finally, mycoplasmal infections have been present before mankind evolved, but they were rarely identified as human pathogens until recently, and they are now recognized as important coinfections that are able to modify the course and prognosis of various infectious diseases and other chronic illnesses. The infectious processes caused by these intracellular microorganisms are examined as well as some general aspects of their pathogeneses, clinical presentations, and diagnoses. We will finally consider examples of treatments that have been used to reduce morbidity and mortality of these infections and discuss briefly the current status of vaccines, in particular, against the SARS-CoV-2 virus. It is important to understand some of the basic features of these emerging infectious diseases and the pathogens involved in order to better appreciate the contributions of this special issue on how infectious diseases can affect human pregnancy, fetuses and neonates. Laboratory of Ion Channels Biological Membranes and Cell Signaling Department of Biophysics Faculty of Medicine Universidad de la República Department of Infectious Diseases Faculty of Medicine Universidad de la República Cellular and Molecular Physiology Laboratory (CMPL) Department of Obstetrics Division of Obstetrics and Gynaeology School of Medicine Faculty of Medicine Pontificia Universidad Católica de Chile Department of Physiology Faculty of Pharmacy Universidad de Sevilla Medical School (Faculty of Medicine) São Paulo State University (UNESP) University of Queensland Centre for Clinical Research (UQCCR) Faculty of Medicine and Biomedical Sciences University of Queensland Department of Pathology and Medical Biology University of Groningen University Medical Center Groningen (UMCG) Department of Molecular Pathology The Institute for Molecular Medicine Medical School (Faculty of Medicine) São Paulo State University (UNESP) Fondo Nacional de Desarrollo Científico y Tecnológico: 1190316

Highlights • COVID-19 is a common pathology that may affect diverse organs, including the central and peripheral nervous system. • Coronaviruses have important neurotropic potential and they cause neurological alterations that range from mild to severe. • CoV may affect any age group; the main symptoms are headache, dizziness, and altered consciousness. • The neurological symptoms caused by CoV (MERS-CoV, SARS-CoV and SARS-CoV2) are similar., Objective To describe the main neurological manifestations related to coronavirus infection in humans. Methodology A systematic review was conducted regarding clinical studies on cases that had neurological manifestations associated with COVID-19 and other coronaviruses. The search was carried out in the electronic databases PubMed, Scopus, Embase, and LILACS with the following keywords: “coronavirus” or “Sars-CoV-2” or “COVID-19” and “neurologic manifestations” or “neurological symptoms” or “meningitis” or “encephalitis” or “encephalopathy,” following the Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results Seven studies were included. Neurological alterations after CoV infection may vary from 17.3% to 36.4% and, in the pediatric age range, encephalitis may be as frequent as respiratory disorders, affecting 11% and 12% of patients, respectively. The Investigation included 409 patients diagnosed with CoV infection who presented neurological symptoms, with median age range varying from 3 to 62 years. The main neurological alterations were headache (69; 16.8%), dizziness (57, 13.9%), altered consciousness (46; 11.2%), vomiting (26; 6.3%), epileptic crises (7; 1.7%), neuralgia (5; 1.2%), and ataxia (3; 0.7%). The main presumed diagnoses were acute viral meningitis/encephalitis in 25 (6.1%) patients, hypoxic encephalopathy in 23 (5.6%) patients, acute cerebrovascular disease in 6 (1.4%) patients, 1 (0.2%) patient with possible acute disseminated encephalomyelitis, 1 (0.2%) patient with acute necrotizing hemorrhagic encephalopathy, and 2 (1.4%) patients with CoV related to Guillain-Barré syndrome. Conclusion Coronaviruses have important neurotropic potential and they cause neurological alterations that range from mild to severe. The main neurological manifestations found were headache, dizziness and altered consciousness.

Graphical abstract, Highlights • Virus-induced infections like SARS-CoV-2 is a serious threat to human health and economics. • SARS-CoV-2 sheds out through stools making a possible faecal-oral route of transmission to environment matrix. • Detection of enteric viruses in the environmental samples is extremely challenging. • Integrating two or more disinfection strategies provides an effective inactivation method for viral pathogens., The unprecedented global spread of the severe acute respiratory syndrome (SARS) caused by SARS-CoV-2 is depicting the distressing pandemic consequence on human health, economy as well as ecosystem services. So far novel coronavirus (CoV) outbreaks were associated with SARS-CoV-2 (2019), middle east respiratory syndrome coronavirus (MERS-CoV, 2012), and SARS-CoV-1 (2003) events. CoV relates to the enveloped family of Betacoronavirus (βCoV) with positive-sense single-stranded RNA (+ssRNA). Knowing well the persistence, transmission, and spread of SARS-CoV-2 through proximity, the faecal-oral route is now emerging as a major environmental concern to community transmission. The replication and persistence of CoV in the gastrointestinal (GI) tract and shedding through stools is indicating a potential transmission route to the environment settings. Despite of the evidence, based on fewer reports on SARS-CoV-2 occurrence and persistence in wastewater/sewage/water, the transmission of the infective virus to the community is yet to be established. In this realm, this communication attempted to review the possible influx route of the enteric enveloped viral transmission in the environmental settings with reference to its occurrence, persistence, detection, and inactivation based on the published literature so far. The possibilities of airborne transmission through enteric virus-laden aerosols, environmental factors that may influence the viral transmission, and disinfection methods (conventional and emerging) as well as the inactivation mechanism with reference to the enveloped virus were reviewed. The need for wastewater epidemiology (WBE) studies for surveillance as well as for early warning signal was elaborated. This communication will provide a basis to understand the SARS-CoV-2 as well as other viruses in the context of the environmental engineering perspective to design effective strategies to counter the enteric virus transmission and also serves as a working paper for researchers, policy makers and regulators.

The widespread coronavirus SARS-CoV-2 has already infected over 4 million people worldwide, with a death toll over 280,000. Current treatment of COVID-19 patients relies mainly on antiviral drugs lopinavir/ritonavir, arbidol, and remdesivir, the anti-malarial drugs hydroxychloroquine and chloroquine, and traditional Chinese medicine. There are over 2,118 on-going clinical trials underway, but to date none of these drugs have consistently proven effective. Cathepsin L (CatL) is an endosomal cysteine protease. It mediates the cleavage of the S1 subunit of the coronavirus surface spike glycoprotein. This cleavage is necessary for coronavirus entry into human host cells, virus and host cell endosome membrane fusion, and viral RNA release for next round of replication. Here we summarize data regarding seven CatL-selective inhibitors that block coronavirus entry into cultured host cells and provide a mechanism to block SARS-CoV-2 infection in humans. Given the rapid growth of the SARS-CoV-2-positive population worldwide, ready-to-use CatL inhibitors should be explored as a treatment option. We identify ten US FDA-approved drugs that have CatL inhibitory activity. We provide evidence that supports the combined use of serine protease and CatL inhibitors as a possibly safer and more effective therapy than other available therapeutics to block coronavirus host cell entry and intracellular replication, without compromising the immune system., Key messages • There are over 2118 on-going clinical trials for COVID-19 patients, but current results are limited. • Host cell membrane CatL and TMPRSS2 promote coronavirus cell entry by removing the virus surface spike protein S1 subunit. • In host cell endosomes, CatL removes the S1 subunit and promotes viral membrane fusion, viral RNA release, and replication. • At least 7 CatL-selective inhibitors effectively block coronavirus infection of human cells. • At least 10 US FDA-approved drugs exert CatL inhibitory activity. • Combined use of TMPRSS2 inhibitor camostat and CatL inhibitors or FDA-approved CatL inhibitory drugs merits consideration for urgent testing in COVID-19 patients. • Chloroquine-induced endosomal pH increase and protease inactivation inhibit coronavirus infection, but impair human adaptive immunity. • The protease inhibitor cocktail therapy proposed here could block coronavirus infection while sparing human adaptive immunity.