Path to another drug against COVID-19 The rapid development of vaccines has been crucial in battling the ongoing COVID-19 pandemic. However, access challenges remain, breakthrough infections occur, and emerging variants present increased risk. Developing antiviral therapeutics is therefore a high priority for the treatment of COVID-19. Some drug candidates in clinical trials act against the viral RNA-dependent RNA polymerase, but there are other viral enzymes that have been considered good targets for inhibition by drugs. Owen et al . report the discovery and characterization of a drug against the main protease involved in the cleavage of polyproteins involved in viral replication. The drug, PF-07321332, can be administered orally, has good selectivity and safety profiles, and protects against infection in a mouse model. In a phase 1 clinical trial, the drug reached concentrations expected to inhibit the virus based on in vitro studies. It also inhibited other coronaviruses, including severe acute respiratory syndrome coronavirus 1 and Middle East respiratory syndrome coronavirus, and could be in the armory against future viral threats. —VV

The worldwide outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become an established global pandemic. Alongside vaccines, antiviral therapeutics are an important part of the healthcare response to counter the ongoing threat presented by COVID-19. Here, we report the discovery and characterization of PF-07321332, an orally bioavailable SARS-CoV-2 main protease inhibitor with in vitro pan-human coronavirus antiviral activity, and excellent off-target selectivity and in vivo safety profiles. PF-07321332 has demonstrated oral activity in a mouse-adapted SARS-CoV-2 model and has achieved oral plasma concentrations exceeding the in vitro antiviral cell potency, in a phase I clinical trial in healthy human participants. Clinical Trial Registration ID #: NCT04756531

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We relate the performance of mutual fund trades to their motivation. A fund manager who believes that a stock is significantly mispriced will want to trade in its shares.However, heavy investor outflows (inflows) will constrain the manager by forcing him or her to control liquidity by selling (buying) stocks. Our results support the hypotheses that managers possess a greater ability to value stocks than previously observed and that trade motivation matters when assessing this ability. Valuation-motivated buys outperform their benchmarks by significant margins, but liquidity-motivated buys underperform. A similar, but weaker, pattern is found for stocks that funds sell. Does Motivation Matter When Assessing Trade Performance? An Analysis of Mutual FundsManagers of actively managed mutual funds buy and sell stocks for different reasons. Chief among their motivations is to generate trading profits based on valuation beliefs. However, the structure of open-end funds also leads fund managers to trade for other reasons. First, unanticipated investor flows force fund managers to continually rebalance their portfolios in order to control liquidity. 1 Second, a desire to minimize taxable distributions creates incentives for fund managers to sell losers heading into their tax year-end. 2 Finally, aspiring to impress investors, fund managers may window dress their portfolios by buying recent winners and selling recent losers just before reporting dates. 3 In a rational expectations framework, trades primarily motivated by reasons other than valuation beliefs place fund managers in the role of noise traders who should experience losses to informed investors. 4 Under the presumption that fund managers possess the ability to value stocks, these liquidity, tax, and window dressing trades should thus underperform valuation-based trades.In this paper, the performance of mutual fund trades is related to their motivation.By segmenting trades based on motivation, we make a contribution to the literature that examines fund structures by comparing the subsequent performance of valuation-and liquidity-motivated trades.

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