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Inflammation is generally accepted as a component of the host defence system and a protective response in the context of infectious diseases. However, altered inflammatory responses can contribute to disease in infected individuals. Many endogenous mediators that drive the resolution of inflammation are now known. Overall, mediators of resolution tend to decrease inflammatory responses and provide normal or greater ability of the host to deal with infection. In the lung, it seems that pro-resolution molecules, or strategies that promote their increase, tend to suppress inflammation and lung injury and facilitate control of bacterial or viral burden. Here, we argue that the demonstrated anti-inflammatory, pro-resolving, anti-thrombogenic and anti-microbial effects of such endogenous mediators of resolution may be useful in the treatment of the late stages of the disease in patients with COVID-19.

Many drugs are being developed and clinically tested for treating COVID-19. The knowledge of the targets and the properties of these drugs are highly useful for facilitating the drug repurposing, clinical evaluation, and drug & target discovery efforts. A variety of databases have provided the dedicated information sources and access facilities to support these efforts. The main features of these databases are described.

The COVID‐19 pandemic caused by new betacoronavirus SARS‐Cov‐2 demands rapid exploration of safe and effective therapeutic options. In this perspective, “drug repurposing” aims to represent a rapid and valuable strategy. In the last decades, the endogenous gasotransmitter hydrogen sulfide (H2S) has emerged as a ubiquitous modulator of several biological functions. Early studies pointed out its importance in the regulation of numerous biological functions and systems. Accordingly, H2S deficiency has been associated with several disorders, and many chemotypes of H2S‐releasing agents have been developed as potential therapeutic tools for diseases related with impaired H2S production/activity. Some of these compounds are in advanced clinical trials. Presently, the pivotal role of H2S in modulating the inflammatory response and proinflammatory cytokine cascade is well recognized, and the usefulness of some H2S‐donors for the treatment of different forms of acute lung inflammation (due to infectious and non‐infectious etiologies) has been reported. More recent evidence is also unravelling several mechanisms of action which may account for antiviral effects of this gasotransmitter. Noteworthy, some preliminary clinical results suggest an inverse relationship between endogenous H2S levels and severity of COVID‐19 disease. Therefore, repurposing of H2S‐releasing drugs may be worthy of investigation as potential therapeutic opportunities for treatment of COVID‐19 disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the novel coronavirus disease 2019 (COVID-19), a highly pathogenic and sometimes fatal respiratory disease responsible for the current 2020 global pandemic. Presently, there remains no effective vaccine or efficient treatment strategies against COVID-19. Non-steroidal anti-inflammatory drugs (NSAIDs) are medicines very widely used to alleviate fever, pain, and inflammation (common symptoms of COVID-19 patients) through effectively blocking production of prostaglandins (PGs) via inhibition of cyclooxyganase enzymes. PGs can exert either proinflammatory or anti-inflammatory effects depending on the inflammatory scenario. In this review, we survey the potential roles that NSAIDs and PGs may play during SARS-CoV-2 infection and the development and progression of COVID-19. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.

Identifying drugs effective in the new coronavirus disease 2019 (COVID-19) is crucial, pending a vaccine against SARS-CoV2. We suggest the hypothesis that cannabidiol (CBD), a non-psychotropic phytocannabinoid, has the potential to limit the severity and progression of the disease for several reasons:- (a) High-cannabidiol Cannabis sativa extracts are able to down-regulate the expression of the two key receptors for SARS-CoV2 in several models of human epithelia, (b) cannabidiol exerts a wide range of immunomodulatory and anti-inflammatory effects and it can mitigate the uncontrolled cytokine production responsible for acute lung injury, (c) being a PPARγ agonist, it can display a direct antiviral activity and (d) PPARγ agonists are regulators of fibroblast/myofibroblast activation and can inhibit the development of pulmonary fibrosis, thus ameliorating lung function in recovered patients. We hope our hypothesis, corroborated by preclinical evidence, will inspire further targeted studies to test cannabidiol as a support drug against the COVID-19 pandemic. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.

Coronavirus disease 2019 (COVID-19), the disease resulting from infection by a novel coronavirus, SARS-Cov2, has rapidly spread since November 2019 leading to a global pandemic. SARS-Cov2 has infected over four million people and caused over 290,000 deaths worldwide. Although most cases are mild, a subset of patients develop a severe and atypical presentation of acute respiratory distress syndrome (ARDS) that is characterised by a cytokine release storm (CRS). Paradoxically, treatment with anti-inflammatory agents and immune regulators has been associated with worsening of ARDS. We hypothesize that the intrinsic circadian clock of the lung and the immune system may regulate individual components of CRS, and thus, chronotherapy may be used to effectively manage ARDS in COVID-19 patients. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.

This is the peer reviewed version of the following article: "Statins: Could an old friend help the fight against COVID-19?" . British Journal of Pharmacology (2020): 19 June, which has been published in final form at https://doi.org/10.1111/bph.15166. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions, he COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has overwhelmed healthcare systems requiring the rapid development of treatments, at least, to reduce COVID-19 severity. Drug repurposing offers a fast track. Here, we discuss the potential beneficial effects of statins in COVID-19 patients based on evidence that they may target virus receptors, replication, degradation, and downstream responses in infected cells, addressing both basic research and epidemiological information. Briefly, statins could modulate virus entry, acting on the SARS-CoV-2 receptors, ACE2 and CD147, and/or lipid rafts engagement. Statins, by inducing autophagy activation, could regulate virus replication or degradation, exerting protective effects. The well-known anti-inflammatory properties of statins, by blocking several molecular mechanisms, including NF-κB and NLRP3 inflammasomes, could limit the "cytokine storm" in severe COVID-19 patients which is linked to fatal outcome. Finally, statin moderation of coagulation response activation may also contribute to improving COVID-19 outcomes, This work and data discussed here were supported by grants from the Instituto de Salud Carlos III (ISCIII) and Fondos FEDER European Union (PI17/00119 and Red de Investigación Renal (REDINREN): RD16/0009, to M.R-O, PI17/01495 to J.E, PI18/01133 to AMR, PI19/00815 to A.O); Comunidad de Madrid (“NOVELREN” B2017/BMD3751 to M.R-O, B2017/BMD-3686 CIFRA2-CM to A.O); Spanish Ministry of Economy and Competitiveness MINECO (DTS17/00203, DTS19/00093) to J,E; “Convocatoria Dinamización Europa Investigación 2019” MINECO (EIN2019-103294 to M.R-O and SR-M); ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071) and DTS18/00032 to A.O; The “Sara Borrell” postdoctoral training program of the ISCIII supported the salary of SR-M (CD19/00021), IMPROVE-PD project (“Identification and Management of Patients at Risk–Outcome and Vascular Events in Peritoneal Dialysis”) funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant Agreement No. 812699 to M.R.O.

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a newly identified coronavirus which has spread from China to the rest of the world causing the pandemic coronavirus disease 19 (COVID‐19). It has fatality rate that floats from 5 to 15% and the symptoms are fever, cough, myalgia and/or fatigue up to dyspnea, responsible for hospitalization and in most of the cases of artificial oxygenation. In the attempt to understand how the virus spreads and how to pharmacologically abolish it, it was highlighted that SARS‐CoV‐2 infects human cells by means of angiotensin converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2) and SARS‐CoV‐2 main protease (Mpro). Once bound to its receptor ACE2, the other two proteases, in concert with the receptor‐mediated signaling, allow virus replication and spread throughout the body. Our attention has been focused on the role of ACE2 in that its blockade by the virus increases Bradykinin and its metabolites, well known to facilitate inflammation in the lung (responsible for cough and fever), facilitate both the coagulation and complement system, three mechanisms that are typical of angioedema, cardiovascular dysfunction and sepsis, pathologies which symptoms occur in COVID‐19 patients. Thus, we propose to pharmacologically block the kallikrein‐kinin system upstream bradykinin and the ensuing inflammation, coagulation and complement activation by means of lanadelumab, which is a clinically approved drug for hereditary angioedema.

Several lines of evidence support a link between the essential element zinc and the coronavirus disease 2019 (COVID-19). An important fact is that zinc is present in proteins of humans and of viruses. Some zinc sites in viral enzymes may serve as drug targets and may liberate zinc ions, thus leading to changes in intracellular concentration of zinc ions, while increased intracellular zinc may induce biological effects in both the host and the virus. Drugs such as chloroquine may contribute to increased intracellular zinc. Moreover, clinical trials on the use of zinc alone or in addition to other drugs in the prophylaxis/treatment of COVID-19 are ongoing. Thereby, we aim to discuss the rationale for targeting zinc metalloenzymes as a new strategy for the treatment of COVID-19. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.

Lopinavir combined with ritonavir were reported to benefit the patients with SARS by reducing the viral loads. However, in the latest clinical trials, no benefit was observed with lopinavir-ritonavir treatment beyond standard care in patients with COVID-19. We comment here that this disappointed result of clinical trial might result from the low volume of the lung distribution of lopinavir. The major reasons were listed below: 1) The binding affinity of ACE2 with SARS-CoV-2 spike protein is ~10- to 20-fold higher than the binding affinity of ACE2 with SARS-CoV spike protein, indicating that SARS-CoV-2 can enter AT2 cells in lung much easier than SARS-CoV. Therefore, the viral loads of SARS-CoV-2 might be much higher than viral loads of SARS-CoV in the lung tissue. 2) The concentration of lopinavir in the lung tissue was 1.18 μg equiv/ml in rats. The low volume of the lung distribution of lopinavir might not be enough to inhibit the coronavirus replication due to the high viral loads in the lung tissue. 3) In contrast, the concentration of chloroquine in the lung tissue was much higher (30.76 ± 0.85 μg equiv/ml) in rats, which might lead to its clinical and virologic benefits in the treatment of COVID-19 patients. Together, we proposed here that anti-SARS-CoV-2 drug repurposing studies should pay more attentions to the lung tissue distribution of antiviral drugs. The efficacy of antiviral drugs might depend on their lung tissue distributions

Severe pneumonia which shares several of the features of acute respiratory distress syndrome (ARDS) is the main cause of morbidity and mortality in Coronavirus disease 19 (Covid‐19) for which as of now there is no effective treatment. ARDS is caused and sustained by an uncontrolled inflammatory activation characterized by a massive release of cytokines (cytokine storm), diffuse lung edema, inflammatory cell infiltraton and disseminated coagulation. Macrophage and T lymphocyte dysfunction plays a central role in this syndrome. In several experimental in vitro and in vivo models, many of these pathophysiological changes are triggered by stimulation of the P2X7 receptor. We hypothesize that this receptor might be an ideal candidate to target in Covid‐19‐associated severe pneumonia.