Importance The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection. Observations No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19. Conclusions and Relevance The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.

https://jamanetwork.com/journals/jama/articlepdf/2764727/jama_sanders_2020_rv_200005.pdf

Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review.

A novel infectious disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was detected in Wuhan, China, in December 2019. The disease (COVID-19) spread rapidly, reaching epidemic proportions in China, and has been found in 27 other countries. As of February 27, 2020, over 82,000 cases of COVID-19 were reported, with > 2800 deaths. No specific therapeutics are available, and current management includes travel restrictions, patient isolation, and supportive medical care. There are a number of pharmaceuticals already being tested [1, 2], but a better understanding of the underlying pathobiology is required. In this context, this article will briefly review the rationale for angiotensin-converting enzyme 2 (ACE2) receptor as a specific target.

/pdf/angiotensin-converting-enzyme-2-ace2-as-a-sars-cov-2-3drxdjxi93.pdf

Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target.

SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.

The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro.

Therapeutic options in response to the 2019-nCoV outbreak are urgently needed. Here, we discuss the potential for repurposing existing antiviral agents to treat 2019-nCoV infection (now known as COVID-19), some of which are already moving into clinical trials. Therapeutic options in response to the 2019-nCoV outbreak are urgently needed. Here, we discuss the potential for repurposing existing antiviral agents to treat 2019-nCoV infection (now known as COVID-19), some of which are already moving into clinical trials.

Therapeutic options for the 2019 novel coronavirus (2019-nCoV).

Since the first antiviral drug, idoxuridine, was approved in 1963, 90 antiviral drugs categorized into 13 functional groups have been formally approved for the treatment of the following 9 human infectious diseases: (i) HIV infections (protease inhibitors, integrase inhibitors, entry inhibitors, nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and acyclic nucleoside phosphonate analogues), (ii) hepatitis B virus (HBV) infections (lamivudine, interferons, nucleoside analogues, and acyclic nucleoside phosphonate analogues), (iii) hepatitis C virus (HCV) infections (ribavirin, interferons, NS3/4A protease inhibitors, NS5A inhibitors, and NS5B polymerase inhibitors), (iv) herpesvirus infections (5-substituted 2'-deoxyuridine analogues, entry inhibitors, nucleoside analogues, pyrophosphate analogues, and acyclic guanosine analogues), (v) influenza virus infections (ribavirin, matrix 2 protein inhibitors, RNA polymerase inhibitors, and neuraminidase inhibitors), (vi) human cytomegalovirus infections (acyclic guanosine analogues, acyclic nucleoside phosphonate analogues, pyrophosphate analogues, and oligonucleotides), (vii) varicella-zoster virus infections (acyclic guanosine analogues, nucleoside analogues, 5-substituted 2'-deoxyuridine analogues, and antibodies), (viii) respiratory syncytial virus infections (ribavirin and antibodies), and (ix) external anogenital warts caused by human papillomavirus infections (imiquimod, sinecatechins, and podofilox). Here, we present for the first time a comprehensive overview of antiviral drugs approved over the past 50 years, shedding light on the development of effective antiviral treatments against current and emerging infectious diseases worldwide.

/pdf/approved-antiviral-drugs-over-the-past-50-years-4if2c1n8se.pdf

Approved Antiviral Drugs over the Past 50 Years

Chicory (Cichorium intybus L.) is a perennial herb that has been used as a forage for livestock in many parts of the world. Forage chicory produces a large quantity of high quality feed in the warm season under favorable conditions. Animal performance on chicory is similar to that on legumes and superior to grass‐based pastures. In addition, grazing chicory can decrease some internal parasites in livestock, and therefore has potential to reduce the use of anthelmintics. Being a deep‐rooted perennial herb, chicory can reduce nitrate leaching, deep drainage, thereby reducing the rate of soil acidification and the occurrence of dryland salinity. This paper reviews the published research work on the agronomic characteristics, herbage production, grazing management, persistence under grazing, nutritive value, and animal performance of forage chicory, as well as the problems encountered when incorporating chicory into farming systems.

Forage Chicory (Cichorium intybus L.): A Review of Its Agronomy and Animal Production

In addition to its important influence on soil quality and therefore crop productivity, soil organic carbon (SOC) has also been identified as a possible C sink for sequestering atmospheric carbon dioxide. Limited data are available on the impact of management practices on the rate of SOC change in agricultural soils in Australia. In this paper, results of three long-term trials (13–25 years) located near Wagga Wagga in temperate Australia were used to assess C dynamics under different tillage and stubble management practices, and under cropping intensities in pasture/crop rotations. Experimental results confirm the importance of management practices and pasture in determining first the steady-state SOC concentrations that are characteristic of given rotations and crop management systems, and second the rates of change of SOC concentrations as they approach steady-state concentrations in agricultural soils of this agro-ecological zone. A long-term crop/pasture experiment at a site with initial high SOC showed that the rate of SOC change in different treatments ranged from –278 to +257 kg C/ha.year over 0–0.3 m soil depth. Under continuous cropping, even under conservation agriculture practices of no-tillage, stubble retention, and crop rotation, the high initial SOC stock (0–0.3 m) present after a long-term pasture phase was, at best, maintained but tended to decrease with increased tillage or stubble burning practices. The effect of tillage was greater than that of stubble management. Increases in SOC were observed only in rotations incorporating a pasture phase. Our results suggest that improved soil nutrient and grazing management of permanent pasture can lead to an increase of 500–700 kg C/ha.year where the initial SOC concentrations are well below steady-state concentrations that could be expected after long periods of improved management. No difference was found between perennial pasture and annual pasture to the depth measured (0–0.3 m). Our results suggest that pasture holds the key to maintaining, and even increasing, SOC under crop/pasture in this environment.

Guangdi Li

Papers

Therapeutic options for the 2019 novel coronavirus (2019-nCoV).

Approved Antiviral Drugs over the Past 50 Years

Forage Chicory (Cichorium intybus L.): A Review of Its Agronomy and Animal Production

Soil carbon dynamics under different cropping and pasture management in temperate Australia: Results of three long-term experiments

Current therapy for chronic hepatitis C: The role of direct-acting antivirals.