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The antiviral drugs tecovirimat, brincidofovir, and cidofovir are considered for mpox (monkeypox) treatment despite a lack of clinical evidence. Moreover, their use is affected by toxic side-effects (brincidofovir, cidofovir), limited availability (tecovirimat), and potentially by resistance formation. Hence, additional, readily available drugs are needed. Here, therapeutic concentrations of nitroxoline, a hydroxyquinoline antibiotic with a favourable safety profile in humans, inhibited the replication of 12 mpox virus isolates from the current outbreak in primary cultures of human keratinocytes and fibroblasts and a skin explant model by interference with host cell signalling. Tecovirimat, but not nitroxoline, treatment resulted in rapid resistance development. Nitroxoline remained effective against the tecovirimat-resistant strain and increased the anti-mpox virus activity of tecovirimat and brincidofovir. Moreover, nitroxoline inhibited bacterial and viral pathogens that are often co-transmitted with mpox. In conclusion, nitroxoline is a repurposing candidate for the treatment of mpox due to both antiviral and antimicrobial activity.
Background: International travel is a major driver of the introduction and spread of SARS- CoV-2. Aim: To investigate SARS-CoV-2 genetic diversity in the region of a major transport hub in Germany, we characterized the viral sequence diversity of the SARS-CoV-2 variants circulating in Frankfurt am Main, the city with the largest airport in Germany, from the end of October to the end of December 2020. Methods: In total, we recovered 136 SARS-CoV-2 genomes from nasopharyngeal swab samples. We isolated 104 isolates that were grown in cell culture and RNA from the recovered viruses and subjected them to full-genome sequence analysis. In addition, 32 nasopharyngeal swab samples were directly sequenced. Results and conclusion: We found 28 different lineages of SARS- CoV-2 circulating during the study period, including the variant of concern B.1.1.7 (∆69/70, N501Y). Six of the lineages had not previously been observed in Germany. We detected the spike protein (S) deletion ∆69/∆70 in 15% of all sequences, a four base pair (bp) deletion (in 2.9% of sequences) and a single bp deletion (in 0.7% of sequences) in ORF3a, leading to ORF3a truncations. In four sequences (2.9%), an amino acid deletion at position 210 in S was identified. In a single sample (0.7%), both a 9 bp deletion in ORF1ab and a 7 bp deletion in ORF7a were identified. One sequence in lineage B.1.1.70 had an N501Y substitution while lacking the ∆69/70 in S. The high diversity of sequences observed over two months in Frankfurt am Main highlights the persisting need for continuous SARS-CoV-2 surveillance using full-genome sequencing, particularly in cities with international airport connections.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can spread from symptomatic patients with COVID-19, but also from asymptomatic individuals. Therefore, robust surveillance and timely interventions are essential for the control of virus spread within the community. In this regard the frequency of testing and speed of reporting, but not the test sensitivity alone, play a crucial role. In order to reduce the costs and meet the expanding demands in real-time RT-PCR (rRT-PCR) testing for SARS-CoV-2, complementary assays, such as rapid antigen tests, have been developed. Rigorous analysis under varying conditions is required to assess the clinical performance of these tests and to ensure reproducible results. We evaluated the sensitivity and specificity of a recently licensed rapid antigen test using 137 clinical samples in two institutions. Test sensitivity was between 88.2-89.6% when applied to samples with viral loads typically seen in infectious patients. Of 32 rRT-PCR positive samples, 19 demonstrated infectivity in cell culture, and 84% of these samples were reactive with the antigen test. Seven full-genome sequenced SARS-CoV-2 isolates and SARS-CoV-1 were detected with this antigen test, with no cross-reactivity against other common respiratory viruses. Numerous antigen tests are available for SARS-CoV-2 testing and their performance to detect infectious individuals may vary. Head-to-head comparison along with cell culture testing for infectivity may prove useful to identify better performing antigen tests. The antigen test analyzed in this study is easy-to-use, inexpensive, and scalable. It can be helpful in monitoring infection trends and thus has potential to reduce transmission.
The antiviral drugs tecovirimat, brincidofovir, and cidofovir are considered for mpox (monkeypox) treatment despite a lack of clinical evidence. Moreover, their use is affected by toxic side-effects (brincidofovir, cidofovir), limited availability (tecovirimat), and potentially by resistance formation. Hence, additional, readily available drugs are needed. Here, therapeutic concentrations of nitroxoline, a hydroxyquinoline antibiotic with a favourable safety profile in humans, inhibited the replication of 12 mpox virus isolates from the current outbreak in primary cultures of human keratinocytes and fibroblasts and a skin explant model by interference with host cell signalling. Tecovirimat, but not nitroxoline, treatment resulted in rapid resistance development. Nitroxoline remained effective against the tecovirimat-resistant strain and increased the anti-mpox virus activity of tecovirimat and brincidofovir. Moreover, nitroxoline inhibited bacterial and viral pathogens that are often co-transmitted with mpox. In conclusion, nitroxoline is a repurposing candidate for the treatment of mpox due to both antiviral and antimicrobial activity.
Oral swabs, sputum and blood samples from 18 patients with SARS-CoV-2 infection were examined using real-time reverse transcription polymerase chain reaction (RT-PCR) testing. Whereas oral swabs or sputum from the lower respiratory tract were tested RT-PCR positive in all patients, RNAemia was neither detected in 3 patients without symptoms nor in 14 patients with flu-like symptoms, fever or pneumonia. The only patient with RNAemia suffered from acute respiratory distress syndrome (ARDS) and was artificially ventilated in an intensive care unit. Risk for SARS-CoV-2 transmission through blood components in asymptomatic SARS-CoV-2 infected individuals therefore seems negligible but further studies are needed.