2-Thiouridine is a broad-spectrum antiviral nucleoside analogue against positive-strand RNA viruses (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes significant morbidity and mortality worldwide, seriously impacting not only human health but also the global economy. Furthermore, over 1 million cases of newly emerging or re-emerging viral infections, specifically dengue virus (DENV), are known to occur annually. Because no virus-specific and fully effective treatments against these and many other viruses have been approved, they continue to be responsible for large-scale epidemics and global pandemics. Thus, there is an urgent need for novel, effective therapeutic agents. Here, we identified 2-thiouridine (s2U) as a broad-spectrum antiviral nucleoside analogue that exhibited antiviral activity against SARS-CoV-2 and its variants of concern, including the Delta and Omicron variants, as well as a number of other positive-sense single-stranded RNA (ssRNA+) viruses, including DENV. s2U inhibits RNA synthesis catalyzed by viral RNA-dependent RNA polymerase, thereby reducing viral RNA replication, which improved the survival rate of mice infected with SARS-CoV-2 or DENV in our animal models. Our findings demonstrate that s2U is a potential broad-spectrum antiviral agent not only against SARS-CoV-2 and DENV but other ssRNA+ viruses.

Ground-glass opacity caused by the administration of amikacin liposome inhalation suspension: A case report (preprint)

Background: Amikacin liposome inhalation suspension (ALIS) is a key drug for the treatment of refractory Mycobacterium avium complex pulmonary disease (MAC-PD), but causes hypersensitivity pneumonitis in rare cases. Case presentation: A 72-year-old woman was treated with ALIS for refractory MAC-PD. Three weeks later, she was hospitalized for pneumonia. The nose swab PCR test for coronavirus disease 2019, and serum (1,3)-beta-D-glucan test, were negative. Because the opacities worsened after empiric antibiotic therapy, we started corticosteroids, suspecting drug-induced interstitial lung disease (DIILD) caused by ALIS; 3 days later, we found signs of improvement and quickly tapered the corticosteroids. After obtaining informed consent, we performed a drug provocation test of ALIS. Seven days later, she had a re-exacerbation of MAC-ID, leading to a diagnosis of DIILD caused by ALIS. Conclusions: DIILD caused by ALIS is rare, but should be carefully diagnosed because various opacities appear on chest radiograph during the chronic course of the disease.