Natural products continue to be the inspirations for us to discover and acquire new drugs. The seemingly unstoppable viruses have kept records high to threaten human health and well-being. The diversity and complexity of natural products (NPs) offer remarkable efficacy and specificity to target viral infection steps and serve as excellent source for antiviral agents. The discovery and production of antiviral NPs remain challenging due to low abundance in their native hosts. Reconstruction of NP biosynthetic pathways in microbes is a promising solution to overcome this limitation. In this review, we surveyed 23 most prominent NPs (from more than 200 antiviral NP candidates) with distinct antiviral mode of actions and summarized the recent metabolic engineering effort to produce these compounds in various microbial hosts. We envision that the scalable and low-cost production of novel antiviral NPs, enabled by metabolic engineering, may light the hope to control and eradicate the deadliest viruses that plague our society and humanity.

天然产品仍然是我们发现和获取新药的灵感。这些看似势不可挡的病毒不断威胁着人类的健康和福祉。天然产物 (NP) 的多样性和复杂性为针对病毒感染步骤提供了卓越的功效和特异性，并可作为抗病毒药物的极好来源。由于其天然宿主中的丰度较低，抗病毒纳米颗粒的发现和生产仍然具有挑战性。重建微生物中的纳米颗粒生物合成途径是克服这一限制的一个有前途的解决方案。在这篇综述中，我们调查了 23 种最著名的 NP（来自 200 多种抗病毒 NP 候选药物），它们具有独特的抗病毒作用模式，并总结了最近在各种微生物宿主中生产这些化合物的代谢工程工作。我们设想，通过代谢工程实现新型抗病毒纳米颗粒的可扩展和低成本生产，可能会点燃控制和根除困扰我们社会和人类的最致命病毒的希望。