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EstratĂ©gias terapĂȘuticas da COVID-19 : uma abordagem molecular
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Advisor(s)
Abstract(s)
No dia 31 de dezembro de 2019 o Centro de Controlo de Doenças ChinĂȘs reportou um conjunto de casos de pneumonia na cidade de Wuhan com etiologia desconhecida. Em janeiro de 2020, foi sequenciado e isolado o possĂvel agente causador como sendo uma nova estirpe de coronavĂrus, denominada SARS-CoV-2 e, consequentemente, Organização Mundial de SaĂșde (OMS) declarou a epidemia causada por este vĂrus como um problema de saĂșde pĂșblica a nĂvel internacional.
Os coronavĂrus pertencem Ă famĂlia Coronaviridae. Atualmente sabe-se que o SARS-CoV-2 Ă© a sĂ©tima estirpe de coronavĂrus e a quarta pertencente ao gĂ©nero Betacoronavirus que afeta humanos.
O genoma do SARS-CoV-2 Ă© uma molĂ©cula de ĂĄcido ribonucleico nĂŁo segmentado de cadeia positiva com aproximadamente 30 mil bases. Este vĂrus caracteriza-se por apresentar quatro proteĂnas estruturais (spike, S, envelope, E, membrana, M, e nucleocĂĄpside, N) e dezasseis proteĂnas nĂŁo estruturais (NSP, identificadas de 1 a 16). Todas estas proteĂnas desempenham funçÔes importantes na patogĂ©nese da infeção do vĂrus.
O forte investimento na investigação e desenvolvimento de fĂĄrmacos tendo como alvo proteĂnas que desempenham funçÔes cruciais no ciclo de replicação do SARS-CoV-2, nomeadamente nos mecanismos de entrada e de replicação viral, ou fĂĄrmacos que contribuam para a diminuição da resposta imune do hospedeiro, resultarĂĄ na melhoria da eficĂĄcia terapĂȘutica da COVID-19. PorĂ©m, Ă© um processo moroso e incompatĂvel com a urgĂȘncia do atual estado pandĂ©mico. As estratĂ©gias terapĂȘuticas para a COVID-19 recomendadas Ă data pela OMS sĂŁo baseadas no reposicionamento de fĂĄrmacos. Embora apresentem sucesso limitado, estes fĂĄrmacos jĂĄ comercializados com indicaçÔes para outras patologias, tĂȘm permitido algum controlo da progressĂŁo da severidade da doença.
AtĂ© ao dia 24 de setembro de 2021, a OMS publicou sete recomendaçÔes terapĂȘuticas contra a COVID-19, das quais apenas trĂȘs revelaram ter efeitos clĂnicos benĂ©ficos em doentes infetados pelo SARS-CoV-2. A utilização de corticosteroides sistĂ©micos, de inibidores do recetor da interleucina 6 (tocilizumab e sarilumab) e de anticorpos monoclonais neutralizantes (casirivimab e imdevimab) mostraram ser opçÔes eficazes no combate Ă pandemia da COVID-19.
On 31 December 2019, the Chinese Centre for Disease Control reported a cluster of pneumonia cases in Wuhan, China with unknown aetiology. In January 2020, the possible causative agent was sequenced and isolated as a new strain of coronavirus, named SARS-CoV-2 and consequently, World Health Organization (WHO) declared the epidemic caused by this virus as an international public health problem. Coronaviruses belong to the Coronaviridae family. SARS-CoV-2 is now known to be the seventh coronavirus strain and the fourth belonging to the Betacoronavirus genus to affect humans. The genome of SARS-CoV-2 is a non-segmented positive-stranded ribonucleic acid molecule of approximately 30 thousand bases. This virus is characterised by having four structural proteins (spike, S, envelope, E, membrane, M, and nucleocapsid, N) and sixteen non-structural proteins (NSP, identified from 1 to 16). All these proteins play important roles in the pathogenesis of virus infection. The strong investment in research and development of drugs targeting proteins that play crucial roles in the SARS-CoV-2 replication cycle, namely in the viral entry and replication mechanisms, or drugs that contribute to the downregulation of the host immune response, will result in improved therapeutic efficacy of COVID-19. However, this is a lengthy process and incompatible with the urgency of the current pandemic state. The therapeutic strategies for COVID-19 recommended by WHO to date are based on drug repositioning. Although with limited success, these drugs, already marketed with indications for other diseases, have allowed some control of the progression of disease severity. As of 24 September 2021, WHO has published seven therapeutic recommendations against COVID-19, of which only three have been shown to have beneficial clinical effects in patients infected by SARS-CoV-2. The use of systemic corticosteroids, interleukin 6 receptor inhibitors (tocilizumab and sarilumab) and neutralizing monoclonal antibodies (casirivimab and imdevimab) showed to be effective options against the COVID-19 pandemic.
On 31 December 2019, the Chinese Centre for Disease Control reported a cluster of pneumonia cases in Wuhan, China with unknown aetiology. In January 2020, the possible causative agent was sequenced and isolated as a new strain of coronavirus, named SARS-CoV-2 and consequently, World Health Organization (WHO) declared the epidemic caused by this virus as an international public health problem. Coronaviruses belong to the Coronaviridae family. SARS-CoV-2 is now known to be the seventh coronavirus strain and the fourth belonging to the Betacoronavirus genus to affect humans. The genome of SARS-CoV-2 is a non-segmented positive-stranded ribonucleic acid molecule of approximately 30 thousand bases. This virus is characterised by having four structural proteins (spike, S, envelope, E, membrane, M, and nucleocapsid, N) and sixteen non-structural proteins (NSP, identified from 1 to 16). All these proteins play important roles in the pathogenesis of virus infection. The strong investment in research and development of drugs targeting proteins that play crucial roles in the SARS-CoV-2 replication cycle, namely in the viral entry and replication mechanisms, or drugs that contribute to the downregulation of the host immune response, will result in improved therapeutic efficacy of COVID-19. However, this is a lengthy process and incompatible with the urgency of the current pandemic state. The therapeutic strategies for COVID-19 recommended by WHO to date are based on drug repositioning. Although with limited success, these drugs, already marketed with indications for other diseases, have allowed some control of the progression of disease severity. As of 24 September 2021, WHO has published seven therapeutic recommendations against COVID-19, of which only three have been shown to have beneficial clinical effects in patients infected by SARS-CoV-2. The use of systemic corticosteroids, interleukin 6 receptor inhibitors (tocilizumab and sarilumab) and neutralizing monoclonal antibodies (casirivimab and imdevimab) showed to be effective options against the COVID-19 pandemic.
Description
Dissertação para obtenção do grau de Mestre no Instituto Universitårio Egas Moniz
Keywords
SARS-CoV-2 COVID-19 EstratĂ©gias terapĂȘuticas